Good morning, everybody. My name is Suhail Rove, and I am privileged to be the moderator of this Organizing Pneumonia Chest Fleischner Joint Session. Let me clear up some cobwebs that some of you may have about what the Fleischner Society is. The Fleischner Society was formed in 1969 and originally comprised of eight chest radiologists who were interested in pursuing the imaging of chest diseases. Since that time, it has become truly a multidisciplinary international organization comprised, I believe, about 80 members now. And there are chest radiologists predominantly, but there are pulmonologists, and there are thoracic surgeons, and chest pathologists. I think most of us will remember the Fleischner Society's white papers that have been written for the purpose of clarifying topics that are clinically relevant and important where we do not have evidence-based data. For instance, almost 15 years ago, the solitary pulmonary nodules were defined by the Fleischner Society, and there have been multiple other similar publications that have come out. So it has truly done a terrific job in bringing to bear some of the topics that we don't have guidelines on. I am truly very happy and privileged, as I said, to be working with a wonderful faculty. Dr. Kevin Brown needs no introduction. Dr. Kevin Brown is interstitial lung diseases. He is very, very well known in the field. Every guideline that has been written in the field of ILD has been done with him in the forefront, and just as a reflection of how much he is recognized internationally, he is in the incoming presidential leadership of the Fleischner Society and has been writing multiple guidelines. Jen is our pulmonary fellow. She is on my right side here and is very involved with interstitial lung diseases. Jenna Schulner works with me at Lenox Hill Hospital in Manhattan, and she is a PA in the Advanced Lung Diseases Clinic. So we will be beginning by talking about radiographic patterns of organizing pneumonia, a little bit on chest x-ray, but mainly utilizing chest CT scans. We'd like to leave you with the subtypes and etiologies of organizing pneumonia, but basically focus on an algorithmic approach that we as clinicians can utilize for the management of organizing pneumonia, and Kevin will be talking about that. Once we have had these two didactic presentations, we'd like to have our two young colleagues present a clinical case where we can amalgamate all the findings that we have discussed with you and use the algorithmic approach to come up with a diagnosis. Much of what we are going to be talking about is published in Chest last year, entitled Algorithmic Approach, the Diagnosis of Organizing Pneumonia. So let's begin, let's talk a little bit about what is organizing pneumonia, its definitions and types. Now we all know that organizing pneumonia is a clinical radiologic and pathological entity that describes a pattern of tissue repair developing after lung injury, either from a known or an unknown cause. All these years, it has been classified as an interstitial lung disease, however, that is a misnomer because most of the pathology is found at the alveoli or the alveolar ducts. So it should probably be considered a diffuse lung parenchymal disease. It's a rare disease, as you can see the statistics here, if I can get this to work. It ranges from about 2 to 7 per 100,000 cases and the histological findings are described as organizing pneumonia pattern, OPP, which is comprised of a polypoidal plug or plugs of loose connective tissue that are seen mainly in the alveoli and the alveolar ducts. You can see on the right hand panel what has been called as a meson body and that is the polypoidal plug that's seen in the alveoli. Yes, there are histological varieties, we are not going to be talking about them. We will be mainly focusing on cryptogenic organizing pneumonia and secondary organizing pneumonia. So let's talk about the two major clinical types that we break our patients into when this diagnosis is made. So cryptogenic organizing pneumonia is when we do not find a cause for organizing pneumonia after an exhaustive search for different causes. And what are the causes? This is what we are talking. Thank you so much Bruce, perfect, thanks. And what are the causes that we typically look at? They are listed here, infection which could be viral, bacterial or fungal. It could be medications and drug toxicity and the common ones are amiodarone, bleomycin and checkpoint inhibitors. There is also inhalational injuries such as hypersensitivity pneumonitis, such as cocaine inhalation, such as vaping that can give rise to an organizing pneumonia pattern. Aspiration pneumonia can also give rise to organizing pneumonia as can organ transplant, infection-induced lung injuries, especially in breast cancer radiation and almost all different types of rheumatological diseases. So this is where organizing pneumonia is secondary to a known pulmonary insult. However, the organizing pneumonia is the primary pathological process that is found in the lungs. You can have secondary organizing pneumonia, but that may not be the primary pathological process and I'd like to talk to you about two other minor factors here. So organizing pneumonia pattern may be seen on CT scans as a component of other interstitial diseases and that is it could be a minor lesion in the setting of interstitial lung diseases. You may have a UIP, NSIP or a hypersensitivity pneumonitis etiology or you could have any of these entities and acute exacerbation of UIP, NSIP or hypersensitivity pneumonitis. It could also be a minor component seen when there is acute lung injury such as diffuse alveolar damage. And finally, the third type of secondary organizing pneumonia that we need to be cognizant of is when it's a nonspecific reaction to another process that is ongoing in the lungs and that could be adjacent to an area that has lung cancer, it could be adjacent to an area that has an infection like lung abscess, pulmonary infarction, etc. So it's important for us to be able to classify the organizing pneumonias into cryptogenic and secondary and in the secondary know that there are three different ways in which it can manifest. Now, I don't want to spend a lot of time on this. We will proceed further. The important thing for us is to know that the HRCT patterns that are consistent with organizing pneumonia can be either consolidation in 75% of the cases. It could be nodular or it could be linear and reticular. Each of these three patterns comes with its own typical and atypical features. I'm going to go through this quickly because Dr. Brown is going to discuss this in the algorithmic approach. In the predominant consolidation pattern, you can have opacities that are either peripheral or they may be in the peribronchovascular area. That's typical. The atypical is ground glass opacities and crazy paving. This is to give you an example of a person who was a 71-year-old male patient presenting with shortness of breath. The first chest x-ray was done in July 2011 and you can see that there is haziness and opacities in the right upper and mid lung zones. The left side is relatively clear. Almost a year later, the right-sided opacities have disappeared and now you can see fairly dense consolidation that's present on the left side. And then a year after that, it has now migrated on to the right side. I've given the differential diagnoses here and we can talk about that. Other consolidative patterns that we need to be cognizant of is this crazy paving, which is mainly ground glass opacities, interlobular septal thickening, as well as the third component, which is very important, which is intralobular lines. Those three components make the picture a crazy paving picture and this is what the patient had secondary to amiodarone use. More nodular opacities here and more peripheral opacities that you can see. This is a patient who had peribronchovascular consolidation. These are axial contrast enhanced images that you can see and while this is not pathonomic, but in the right clinical scenario, this is another pattern that should lead us to think that we may be dealing with organizing pneumonia. Ground glass opacities, not uncommonly positive on PET scan, usual PET scan uptake, maybe about five to six, as seen in a study by Erdogan that was published in the Journal of Nuclear Medicine many years ago. The second pattern that I want to leave you with is predominantly nodular pattern, micro or macro nodules or even masses, solitary or multiple. And then the atypical is the centrilobular or the tree and bud opacities. Now all of you would say this looks suspicious. I want to rule out the possibility of lung cancer in a 73-year-old male smoker. The pretest probability, Brock's calculator, is about 40%. Is this malignant? And on biopsy, it was proven to be organizing pneumonia. This is another patient in whom a surgical biopsy was performed and we can see that these are small subcentimeter nodules that are present, larger nodules and masses that are present in this image and definitely a mass that you can see in the third image. And the last thing I wanted to leave you with are the linear and reticular patterns. Now this is a patient who had a biopsy proven organizing pneumonia and you can see that there are parenchymal bands that are present at the bases of the lungs in the lower lobe. A year later, the parenchymal bands had resolved very significantly, but there is some linear atelectasis, etc. So it may take a long time for these to resolve. This is an interesting sign, which is the reverse halo or the atoll sign. And this is a 32-year-old male patient who had chronic persistent cough and shortness of breath lasting for a year with a 20-pound weight loss. And you can see these areas of central ground glass opacity completely surrounded by this peripheral consolidative rim and this is what is called reversed halo or atoll sign. And then the last two slides I have show you extensive ground glass opacity in the 74-year-old patient following four days of onset of shortness of breath, extensive ground glass opacities. A couple of years later, you can see that most of the ground glass opacities have resolved. Left in its place is more of a reticulation, coarse reticular pattern that is visible and that is how many of the ground glass opacities heal. This is a perilobular thickening, also called an arcade pattern, which is interesting in a 67-year-old morbidly obese male patient, which we are seeing the images of, progressive shortness of breath, CT done through the lung bases show a combination of bronchiolectasis. Also we see these areas of centrilobular clearing, but there is a peribronchiolar fibrosis and this is this perilobular thickening, which is visible here as you can see, is what has been called the arcade sign. Again, not pathonomic, but suggestive that there may have been an NSIP pattern and organizing pneumonia following. I'm going to stop here. Thank you so much and I request Kevin to... Well, good morning. Thanks for showing up today, particularly since it's such a nice day outside. So I'm Kevin Brown. I'm a lung doctor from Denver and I've been doing this for a while and it's been my pleasure actually to work with Suhail Rude for actually much longer than I would like to acknowledge. And I think those of you who know him would appreciate that you will not find a more complete and thoughtful physician anywhere in this country and probably as importantly, you probably won't find a pulmonologist who knows radiology better than he does. And I point that out because this is a really important issue. So at my place, we have the luxury of having folks that are dedicated, radiologists who are dedicated to looking at the chest, but most of you won't have that access. So you can imagine when you're asking someone who just looked at an MRI of the brain and just got out and washed up from a barium enema and looked at the ultrasound of the lower extremity, then showing them a high resolution CT scan of the chest and thinking about a disease that occurs in two in 100,000 patients and asking the question, what is this? We all have to get better at thinking about diffuse lung disease as pulmonologists because we see it much more than radiologists do. So here are my conflict of interest. None of these are relevant for this talk. So this is the algorithm that was included in the paper that Professor Ruef alluded to and I'm going to go through this actually quite quickly because what we want to do is we want to get to the cases and think about how we can put this into practice. So when a patient comes to you with a clinical syndrome potentially explained by the presence of organizing pneumonia, what we do is we take the combination of the clinical context and the plain chest radiographic features. We've got to put something together to think about this and what does that clinical context look like? So what do we think about when we're thinking about the things that could be associated with the presence of organizing pneumonia? So constitutional symptoms, right? Night sweats, right? Somebody who's been sick but persistent night sweats, fever, cough, dyspnea, other respiratory symptoms and an underlying diagnosis. This is the separation between the primary or the cryptogenic form of organizing pneumonia and the secondary form, right? Some underlying diagnosis that we know is associated with or complicated by the presence of organizing pneumonia in the lung. Laboratory findings are nonspecific but often abnormal, not abnormal enough in a way that can give you a specific diagnosis but not completely normal. But where are the features that help us understand where organizing pneumonia occurs? It's in the plain chest radiograph, right? Persistent pneumonia and migratory infiltrates are two of the biggest things. And new focal parenchymal opacities that are unresponsive, particularly to antibiotic therapy that we would either think about. So what does that look like, right? Migratory parenchymal opacities over time, over a few weeks, over a few months. Sarouf showed you a case that occurred over years occurring as organizing pneumonia. So how do we think about those in overall context? He alluded to the issue of cryptogenic and the presence of organizing pneumonia is the only other explanation, the underlying pathologic identifier in a patient with an idiopathic interstitial pneumonia. Now the key here is that everybody's got an idiopathic interstitial pneumonia if you don't ask any more questions, right? Because I don't know why you have it. So the key is that you have to do something active to exclude the presence of some other explanation for the presence of organizing pneumonia. And the importance of that is because your confidence in particular clinical scenarios with particular underlying diagnoses increases when you have a particular diagnosis. For example, dermatomyositis, polymyositis with a parenchymal infiltrate that's consolidated in character in a peripheral or peribronchal vascular manner is likely to be, if once you've excluded infection, likely to be an organizing pneumonia pathologic pattern, right? So it increases your confidence. And Professor Rhodes already undergone associations and causes that are potential, but I would point out the one in particular is a post-infectious or active infection with associated organizing pneumonia that could account for the presence of the underlying pathology. What are those other things that are going to fall within your differential as you think about it, right? These are the patterns organizing acute lung injury, a mixed pattern, a minor component of another ILD. But these are important because you can be confused. Diffuse alveolar damage or an acute exacerbation of an underlying, particularly fibrosing interstitial lung disease. It is not rare to find a radiographic pattern that looks very much like organizing pneumonia, but is relatively resistant to our usual therapy with glucocorticoids. An overlap pattern, particularly of organizing pneumonia, nonspecific interstitial pneumonia or eosinophilic pneumonia. And then a minor component of all these other, particularly fibrosing interstitial lung diseases, but lung cancer not to be excluded. All right. So you've defined the clinical context and you've worked really hard to try to find something other than a cryptogenic or idiopathic interstitial pneumonia, right? That's not the default diagnosis. It's a diagnosis of exclusion. You've worked hard to do that. You have a plain chest radiograph that suggests that there's a problem, right? So now you get a high-resolution CT scan. This gets better every day. We have a new single-photon counting CT scanner at my place, and it's almost like pathology. So we're going to get better and better at this, and you're going to get better and better at it because you're going to see these patients and you're going to understand the patterns that go along with the clinical context. So just briefly, because he's already alluded to these, the predominant consolidative, the peripheral consolidation, which is the classic characteristic pattern or the peribronchovascular consolidation, again, a common pattern, particularly in underlying connective or autoimmune diseases. Ground glass opacity, and I just want to highlight something he alluded to previously is that when you do a PET scan on these, as well as on some of the nodules, organizing pneumonia can be hot, right? So I can't fully exclude the presence of organizing pneumonia, as well, and the crazy paving. The nodules, right? Multiple subsonometer nodules, a single large nodule. You're always worried about lung cancer in this setting, and the peripheral mass with consolidated features, and the linear reticular stuff, right? These parenchymal bands, which I always find very troubling, and frequently default to thinking that it's some sort of previous pulmonary vascular abnormality, but I cannot exclude the presence of organizing pneumonia, and again, the reverse halo atol sign. All right. So what have you done? You've created the clinical context, and you've either included or excluded the presence of an idiopathic interstitial pneumonia. You've looked at the plain chest radiograph and said, I need a high-resolution CT scan, and then you define the pattern on a high-resolution CT scan, so you can combine that clinical context with the high-resolution imaging pattern, and what you really need to do at that point is ask the radiologist, right? This is the multidisciplinary discussion. This has actually been investigated that more smart people that think about the common problem, the better you are at figuring out what the answer is. So this is not just a default made-up story that occurs in academics. It actually works, and we actually get smarter by sharing information. So we combine the clinical context and the high-resolution CT scan pattern, and we've got to make some sort of diagnostic confidence statement, right? The patient came to you for an answer, and you're trying to figure out what that is. And then the separate question is, how confident can I be, and if I can't be adequately confident, do I need to do an additional test, and almost always that has to do with the bronchoscope or something similar, right? So there are situations where observation alone might be adequate, right? If you have a reasonably confident diagnosis of a patient who's had previous organizing pneumonia, a patient who's got a secondary feature, all right, or secondary underlying cause, maybe amiodarone therapy, maybe polymyositis, that you can be reasonably confident. Patient is clinically stable. There's a very low likelihood of some other bad diagnosis, particularly malignancy, active vasculitis in particular, or infection, those three things in particular. But the important thing is the patient's got to be willing to come back, right? So confident and stable today does not mean stable tomorrow. You might be willing to try empiric therapy, and who are those patients? Those patients are those in whom you are uncomfortable with, or they are uncomfortable with, taking additional steps, right? Ninety-year-old, underlying, other diagnoses, maybe you're uncomfortable doing bronchoscopy, certainly uncomfortable doing surgical lung biopsy because the risks start to outweigh the benefits there. Again, you're thinking about the likelihood of an alternative diagnosis that could be bad for the patient, particularly if you're going to treat with an immunosuppressive therapy, but also the willingness to follow up over time, all right? So what if you can't be confident enough? What are you going to do, right? There's two approaches. Sometimes they're combined. You can use broncho-veal or lavage. Helps exclude infection. Sometimes it helps you with the diagnosis of malignancy, but a tissue diagnosis is often combined and necessary. So if you have to do something additional, what does that mean? Broncho-veal or lavage, again, is not diagnostic in a particular sense. You're going to find a mixed pattern of lymphocytes, neutrophils, and eosinophils, right? You're going to exclude infection by culturing it. You're going to look for cytology to exclude malignancy, if possible. But again, the pattern seen on broncho-veal or lavage is not diagnostic, right? It's helpful, but not diagnostic. But you almost always add in pathology, right? You're going to do bronchoscopy with BAL, trans-bronch, maybe a cryobiopsy if you're using it at your place. We don't do it at our place for a handful of reasons. It may or may not obviate the need for a surgical lung biopsy, and I'm going to touch on this in a second. It's a CT-guided needle, often used with a peripheral nodule, or you may get to a surgical lung biopsy. So why do we think about it? Why do I think about it this way? So here's a trans-bronchial lung biopsy. There's a surgical lung biopsy. Do not be fooled, OK? A trans-bronchial lung biopsy is not a substitute for a surgical lung biopsy, and when we think about diffuse lung disease. We talk as if the entire lung is affected in exactly the same way, but we know that that's not true. Here's a surgical lung biopsy specimen that shows essentially normal lung on the left-hand side of the slide, and a whole bunch of meson bodies filling the alveolar space on the right-hand side. It does not take a lot of imagination to think that you could do a transbronchial lung biopsy and get completely normal lung. All right? So if you're looking for organizing pneumonia and you need a positive diagnosis, you need to make this, you need to think about this. All right, so now you've got the clinical context. You've got a high-resolution CT scan to help you with the pattern, a specific pattern to help you. And if necessary, if you're on the right-hand side of the slide after the initial multidisciplinary review, you have BAL and pathology. You're going to end up in one of three places, right? You're going to say, this is organizing pneumonia, this is cryptogenic organizing pneumonia, or secondary organizing pneumonia, and I'm going to treat. You're going to have a provisional diagnosis, or you're going to have an alternative diagnosis, right? The two extremes are fine. The provisional diagnosis is obviously the issue. And I say, you're going to end up with a definitive or an alternative diagnosis, but that only works when you have longitudinal follow-up. All right, so if you can take anything away from what I've talked about is that the definition of the clinical context is not everybody has an idiopathic interstitial pneumonia. It's that I asked a whole bunch of questions and was able to separate secondary from an idiopathic disorder. And secondly, that longitudinal follow-up is the key to understanding what's going to happen to the patient. With that, I will turn it over to our young colleagues. Thank you very much. My name is Jenna Shulner, and I'm a PA. As Dr. Roof said, I work with him at the Advanced Lung Disease Clinic. And I'll be presenting a case of organizing pneumonia with Dr. Zain Khati. So this is a 64-year-old woman. She has a past medical history of sciatica and atrial fibrillation. She presented with shortness of breath that she had over the past three to four months with acute worsening for the past day. She can only walk about 12 to 15 feet before having to stop. Her oxygen saturation at rest on room air was 82%. She had recently completed a short steroid taper for pinched nerve and associated paresthesias. She presented with acute hypoxemic respiratory failure, and review of symptoms was otherwise negative. She worked with construction and lumber materials for the past 35 years. She has no pets, no allergies, no personal or family history of autoimmune or pulmonary disease. She is a non-smoker, no other environmental exposures, and she recently traveled to Florida. So her vital signs were notable for an oxygen saturation of 94% on two liters of supplemental oxygen, and she has an elevated BMI of 44. Otherwise, her physical exam was normal. So we wanted to provide an X-ray from two months prior, and it's difficult to interpret because of her BMI, but it was felt to be normal, and that's how it was interpreted. So in contrast, this X-ray was upon admission, and this shows bilateral pachy-opacities in more so in the lower lobes. So I invite... Jenna, we have Dr. Shah here. He's a chest radiologist. Rakesh, are you? Because we were wondering if we could get a radiologist to comment on our diagnosis, but not sure, maybe not. Okay. Hi, so continuing the presentation, this is the CT scan that was obtained during this patient's admission. As you go through, and I'll provide still images, you can see some peripheral lacy opacities and some consolidations that coalesce predominantly at the lower lobes in a peribronchovascular distribution. As you go lower in the patient, you seem to see the prior RK pattern that was mentioned in the didactic portion of this. So overall, a pattern that's not really consistent with its alternative to UIP. Dr. Brown, Dr. Raif, do you have any additional comments about this CAT scan? One more thing, as we scroll through the imaging, you can note that there is a significant hiatal hernia in this patient, which comes up posterior to the trachea there. Yeah, so we agree with your analysis extensive ground glass opacities. There is some reticulation important to define the pattern. Much of it is peripheral, but some of it is going towards the central areas. So peribronchovascular. And the important thing is the esophagus is dilated. And if the esophagus is dilated, then we are always concerned when we see what we perceive as fibrotic lung disease. And I think Kevin, you've brought that out in multiple presentations of yours. Important for us to rule out the possibility of chronic aspiration, which can result in CT findings suggestive of fibrotic lung disease. And then if you go down to the bases, you can see, especially on the left side, a perilobular pattern, which is there's a central area of clearing and where the interlobular septa are, they are significantly thickened. And as we mentioned, that that is what is called perilobular fibrosis or archaic pattern seen in many different conditions, but in the right clinical setting, organizing pneumonia is one of them. Also looking at the pulmonary artery, I think that the size of the pulmonary artery did not seem to be prominent on the CT. Kevin, you're? I agree. So what additional workup would you want to see on this patient? I'll tell you what we did after, but if there's anything else. So I just point out the things that I find interesting. So one is the history of atrial fibrillation and whether she'd had therapy in the past for that and what that therapy might be. The fact that she's recently had steroid therapy for both its direct effects and associated adverse effects associated with that. And the BMI and the esophagus for me are important contributor, potential important contributors in this setting, particularly somebody who's, I'm assuming that the sciatica and the requirement for therapy for sciatica suggests that this person is not particularly active or it has not been particularly active at least over the past few weeks to months. Yeah, that would be correct. And regarding her history for atrial fibrillation, she was never on any treatment, including imuterone or any medications that have a significant toxicity that we know of. Zen, one other quick thing. Kevin, I wanted to request you to weigh in on this if you would be so kind. So when we had seen this patient, there was a history, Jenna, that the patient had been exposed to lumbar products and dust for close to 35 years. That's always something that comes up as potentially either aggravating or causing fibrotic lung disease, and especially in the light of the ERJ article that came out a couple of months ago with over 500,000 patients in the UK registry, showing that nitrates, et cetera, or wood exposure, wood dust, et cetera, and particulate matter can all result in either the development of IPF in predisposed individuals or it can result in frequent exacerbations, hospitalizations, and a more prominent progression, more rapid progression. How do you process that information, Kevin? Yeah, so the exposure issue is clearly and is gonna be critical as we think in the future about diffuse lung disease, but I really wanna break down those with the underlying fibrotic disease from those with a more inflammatory lung disease. So those with a fibrotic lung disease, we've actually known for many years, it's just been, I would say, confirmed and further consolidated, that long-term exposure to dust, fumes, et cetera, whether that be in the wood industry or others, is associated with the development of fibrosing lung disease, but that's over a long period of time. Almost assuredly, air pollution is also gonna be a risk factor because we know that from environmental scans that those folks that are in cities, particularly in high-trafficked areas, probably have both a higher prevalence and a higher risk of exacerbation in the fibrotic lung disease. Then there's a group of patients that we're thinking about hypersensitivity pneumonitis, right, a specific allergic reaction within the lung. That exposure can be short or long-term, and then we're thinking about more acute exposures, and those are something bad happening from a normal lung that went bad or a worsening or acute exacerbation of an underlying lung disease. The way I think about, when I'm normally doing the history for exposures, I'm, number one, thinking about hypersensitivity because, right, removing that exposure turns out to be important for the management of the disease, and organizing pneumonia can be a pathologic manifestation of hypersensitivity. And an acute active exposure, such as a drug that might be associated with the active exposure of the disease, but the long-term exposures and the presence, particularly of a fibrosing lung disease, I'm less interested in, only because it doesn't do anything for the patient at that time. It helps me think about why they got it, but it doesn't help me think about how to take care of it. Excellent, thank you. So this person underwent additional workup, which included labs, including connective tissue workup. Listed there, I'll point out the elevated one to 1,280 speckled pattern of the ANA, the indeterminate INCA, an elevated anti-SMITH and anti-RNP, and a low C4, with the remainder of the labs being normal. I'll share the remainder of her workup after, but what do you guys make of these abnormal serologies? Can you keep it on the screen? Yeah, so I'll comment here. So these are clearly abnormal. The ANA from the, just the number, right, is what we would consider outside of the normal range of variation. So what, 5% of middle-aged women will have a positive ANA and no other evidence of active autoimmunity. But almost the vast majority of those patients will have a homogenous ANA of a low titer. So the higher the titer, the more likely an underlying immune disorder exists. Patterns other than homogenous are more likely to be consistent or suggestive of a underlying immune disorder. The anti-SMITH antibody pushes you, the anti-RNP pushes you farther. Unfortunately, it's very rare, purely from the serologies, to come up with a specific diagnosis, right? Almost every rheumatic diagnosis is associated with a combination of clinical features, right, and underlying serologic abnormalities. And in this setting, we have the absence of a clinical syndrome suggestive of an autoimmune disease. I recognize everybody in the room is gonna say, but they've got, right, they've got diffuse lung disease. But it turns out that when you go to the rheumatology literature, almost never is the lung part of the clinical syndrome that makes up a characterizable autoimmune disease. That might change in the future. And as we think about how the lung is involved in underlying rheumatologic disorders, right, we think about it all the time, but the rheumatologists are making the diagnosis on something other than the lung disease. So there's gotta be an underlying clinical scenario consistent with the rheumatic disease, as well as specific serologic abnormalities. And while these are clearly abnormal and suggestive, I don't think they give a specific diagnosis. So can I dwell a little bit on this, Kevin? Because this is something that comes up all the time, and you've very nicely alluded to that. Looking at these values, I would have looked at it, and I would have said, you know, with an ANA titer that is so high, anti-Smith, anti-RNP, which is not just borderline, it's greater than eight, that this is all suggestive of anti, this is suggestive of mixed connective tissue disease. And this is in the setting of a person who has received maybe three weeks of 40, 60 milligrams of prednisone, so anti-DNA antibodies, et cetera, may have become negative. And 10, 20, 30% of the patients will have an autoimmune disease where the musculoskeletal manifestations are not present, and as you alluded to the fact, the lungs are definitely clinically involved. Is it then appropriate for us to say this is most likely an autoimmune disease, autoimmune phenomenon, which has not manifested itself because for mixed connective tissue disease, you do need musculoskeletal, three or four of those other criteria, swelling in the fingers, et cetera. But that would not deter you from saying this is an autoimmune phenomenon, and we should be treating it such? Yeah, I think there are two things to think about here. So I'll give you the response when I go to our rheumatologist and say exactly what you said. Their response is, what the hell are you talking about? So the key is here, right, that I, so I use rheumatology colleagues all the time, and by default, actually, most of the time. And they're stuck somewhat times in the same way we are, which is they have criteria, and it's easy for other people to interpret or misinterpret criteria, but they feel like they're stuck within those. So I would say that in this setting, yeah, in my head, I'm thinking this is probably mixed connective tissue disease, but she's got no clinical manifestations of this disorder other than the lung disease. Now, there's a difference between taking care of the patients and getting the answer right. And I've moved through that stage of my career where I always gotta get the answer right. Yeah. So I'm gonna, so I'm gonna think about this as a patient who's likely to have underlying immune dysfunction. I'd be very confident if somebody said this patient's gonna ultimately develop an underlying autoimmune disease, but is it gonna change my treatment? Because right now, the only thing that I'm treating is the lung disease. There are no other manifestations of her disease that require therapy unless I've misunderstood the case. Thank you, excellent. So we're kind of in that gray area where we don't have a definitive diagnosis yet. So further workup for this patient, she had a MRSA PCR of NERS that was negative, urine Legionella antigen, which was negative. Her COVID was negative. She had a normal echocardiogram with no evidence of pulmonary hypertension, no valvular disease, normal right and left side of the heart. She underwent a bronchoscopy as one would expect as part of the algorithmic approach. We had a very, a cell count with very scant cells. The percentages are listed there. The BAL also grew 7,000 haemophilus parainfluenzae with rare white blood cells. The remainder of the stains for PJP were negative and the cytology was negative for malignant cells. So all roads lead to biopsy. In this patient, we feel very comfortable. She was not on significant oxygen requirements, though she was on oxygen compared to when baseline she was not. Next, I'll show you the pathology images, which were obtained from a transbronchial biopsy here. Here you see a low power view. Dr. Brown, would you like to comment? And then next I'll show you a high power view of the images. Here we're kind of seeing kind of, again, one of the issues with transbronchial biopsy. We worry about the crush artifact. We worry about the inadequacy of the tissue. On this side, you can see a pattern of organized pneumonia with focal fibrin that I think is better demonstrated on the next slide here with those areas of the meson bodies demonstrated here. I've got nothing to add. Very unexpected from a transbronchial biopsy. To me, in my limited experience, but, you know. So what's the differential in this patient? What could she have? I could tell you what we thought, but I would like to hear what you think she thought. Well, you could say, go ahead, because I'll still say whatever I want. At the same time. So again, the same thoughts, you know, is this an underlying connective tissue disease, ILD, CTD-ILD, that's having a flare? Does she have, you know, either fibrotic hypersensitivity pneumonitis with an acute component from her chronic exposure to the lumbar? Does she have organizing pneumonia from an infection and we're just catching it late? Does she have organizing pneumonia from some, you know, cryptogenic organizing pneumonia and we don't know? So I think, in short, we don't know. So did this patient have sleep apnea, just out of interest? No, she was never diagnosed with it. Okay. So, yeah, so infection clearly is a major concern, I think, in this patient who shows up with 24 hours of worsening, who's recently on, presumably, at least moderate dose steroids in that setting. But I could also go to the completely other extreme and say, right, likelihood of an underlying autoimmune disorder with esophageal dysfunction, right, as part of a mixed connective tissue disease or scleroderma-like pattern with a known hiatal hernia and a BMI of 44, that's an extremely high likelihood of recurrent aspiration in this setting, now on steroids, right, and immobile. So I'm completely comfortable with the diagnosis of organizing pneumonia in this setting, and I'm willing to think about it within the context of a disordered immune system. Absolutely. So how would you manage this patient? We ended up treating the patient, so when she was first presented, she did complete a course of IV antibiotics. This was prior to the pathologic diagnosis. As I had stated, she was previously on steroids for her sciatica and her pinched nerve, so she was restarted on the prednisone daily. Because of her continued O2 requirements and lack of clinical improvement, she was transitioned to IV solumedrol, which was tapered back to oral steroids after seven days. Concurrently, she was on prophylactic bactrim. What do you guys think of this kind of need to transition to IV steroids? Was it the right choice? Does she really not respond to steroids or prednisone? Jenna, you want to talk about the rationale? Yeah, so originally the patient was on oral, and then we had had the conversation that the patient was, obviously it was a short period of time, but she was going downhill, six liters. Yeah, so she was needing increased oxygen requirements, so we were concerned with the, even though we didn't know for sure because she didn't have any clinical manifestations of autoimmune disease, we were concerned with those serologies, so we felt it was appropriate to give her higher doses of steroids, and since she was on the prior oral course, we gave her the IV steroids. Yeah, so I think one of the issues was that she had been on the oral prednisone for a few weeks, and there's a small segment of people in whom the conversion of prednisone to prednisolone in the liver may not be happening, and because she was right on the edge requiring four liters of oxygen at rest, six liters when she walked, there was a discussion as to whether or not we should give her intravenous steroids and see if she responds. So that was the rationale. Do you do that in your practice? I don't think this is an uncommon scenario, to tell you the truth, to have quote failed oral prednisone at some modest or low dose and require higher dose or intravenous, right? So there are a group of patients who require intravenous solumedrol who are steroid-resistant, truly steroid-resistant. That occurs, seen more often historically in the asthma patient, but it's absolutely seen in this population as well. And the other thing I'm thinking about, what was her weight? Because in terms of milligrams per kilogram, this would be a relatively small dose. It was underdosed, yeah. Yeah, it would be a relatively small dose. So in a patient who's failing in whom you've excluded infection, I think this would be the right way to go. Sounds good. So in the next couple of minutes, I'll just show you her preceding clinical course, and then we'll leave some time for additional comments and questions. So this was her CAT scan two weeks later after that treatment course. And I'll show you comparative images in the next slide. So as you can see, as we're scrolling down, there's a significant improvement in those consolidations that we had seen previously. There still remains this lacy pattern in the periphery that seems to be worse at the bases, but that initial, the peribronchovascular consolidations seem to have almost completely resolved. On the next image, you'll see comparative images from before and after treatment. On the middle bottom image here, you can see there is some traction bronchiectasis, which may suggest either prior fibrosis or current fibrosis. So as we previously discussed with this excellent discussion by Dr. Brown and Dr. Youth, this was a case that was diagnosed as organizing pneumonia, and that was our clinical suspicion. That's how we treated the patient. Further after that, delineating whether it was a case of cryptogenic organizing pneumonia versus what we suspected was a likely secondary organizing pneumonia due to the following possibilities that we discussed. My personal opinion is that this most likely is related to some CTD-ILD or autoimmune, just because I am fixated on those elevated serologies, recognizing that's a bias that I feel we have as pulmonology. Anyway. Well, you know, the other things, aspiration, post-infectious, et cetera. Kevin, we had felt there was a CT scan that we were able to retrieve from June, and then she was admitted in August. And the CT scan from June was virtually normal. There was no abnormality that was seen. So that's why we were comfortable in saying that this is an underlying autoimmune disease, but for it to progress as rapidly as it did, and we had looked for MDA-5, and all of that had come back negative, we felt that it may be one of the two things that you had mentioned, either infection or aspiration. And that was how we had tried to put the case together. Yeah. I have one question. So she, on her lymphocytes, I think were 10%. She came on prednisone for a short taper. How quickly would you see the lymphocytes drop before a bronchoscopy, when they're on prednisone? It's a really good question. I don't think anybody knows. Yeah, I really don't. We worry about that all the time in hypersensitivity and pneumonitis. I'll tell you that our experience is, my very limited experience is that there is still a marked lymphocyte predominance, even on glucocorticoid therapy. So I don't overly concern myself in somebody who's sick and needs to be initially treated. So I'm comfortable starting treatment and then doing bronchoscopy tomorrow or the next day, if that's what the schedule does. I will say that the neutrophil predominance in this patient on bronchoscopy makes me think, right, number one, infection, number two, aspiration. Thank you, everybody. Thank you.

organizing pneumonia

Fleischner Society

lung disease

tissue repair

lung injury

clinical context

radiographic patterns

diagnosis

management