Good morning, everyone. I'll be presenting a case of airway-centric microscopic polyngitis with a focus on the flow volume loop. My name is Nishna Amanam, and I'm currently an assistant professor in the Department of Pulmonary and Critical Care Medicine at Wake Forest University School of Medicine. I have nothing to disclose. The lesson objectives of this presentation include reviewing clinical manifestations of microscopic polyngitis, so MPA, discussing a case of MPA with tracheobronchial disease manifestations, and recognizing biphasic flow volume loop on PFTs. MPA is a necrotizing vasculitis associated with antineutrophil cytoplasmic antibodies, ANCA, that affects small-sized arteries. Prevalence of MPA ranges from nine to 94 cases per million persons, with an incidence of 0.5 to 24 cases per million person-years. It mainly occurs in the older population, and it does tend to affect both the sexes equally. Patients often present with constitutional symptoms and clinical evidence of glomerulonephritis, upper and lower respiratory tract involvement, and multiple mononeuropathy. Evidence of the airways is demonstrated with either tracheal or bronchial stenosis, while lung parenchyma findings include lung consolidations, pleural effusions, interstitial lung disease, and pulmonary arterial hypertension. Imaging findings in these patients, especially when they have interstitial lung disease, include ground glass opacities, reticulation, traction bronchiectasis, and sometimes honeycombing. Our case is that of a 31-year-old female, G1P0, with a history of subglottic stenosis, status post three subglottic dilations, who presented for another planned dilation of her subglottic stenosis with her ENT. Prior to this, she was seen at a different city under a different institution for her previous dilations. She had no known history of any tracheal injury, previous intubations, or any inflammatory disease that we knew of. When the ENT was performing her procedure, what they noted was there was a possible concern for a left main bronchus occlusion, so our inpatient pulmonary consult team was consulted to do a full bronchoscopy in this patient. During the bronchoscopy, what we noted was that this patient had a complete occlusion of her left main bronchus, complete occlusion of her right upper lobe bronchus, and 25% obstruction of her bronchus intermedius. She did undergo subglottic and left main bronchus balloon dilations with a plan to do her right upper lobe balloon dilation at a later visit. She did get endobronchial biopsies done of the left main bronchus, but unfortunately these were non-revealing. The ones of the subglottic stenosis did demonstrate acute and chronic inflammation with submucosal fibrosis. This is her image of the left main bronchus at the top. It's the one millimeter pinhole, and then the one on the bottom is the right main bronchus. We did end up doing an autoimmune workup that was positive for perinuclear ANCA, so P-ANCA, and she did have elevated anti-myeloperoxidase antibodies, so anti-MPO antibodies. She was diagnosed formally with MPA. What's surprising about this case is that two months prior to her presentation with the ENT, she did actually end up having full PFTs done for exertional dyspnea. At that time, her flow volume loops on those initial PFTs demonstrated a variable extra-thoracic obstruction, and it was thought that this was likely due to her already known history of subglottic stenosis. However, once we did the bronchoscopy, we went back and looked at her initial PFTs, and what we noted was, in fact, that she had a typical biphasic flow volume loop, which was suggestive of a unilateral main stem bronchial obstruction. However, this was not commented upon on the initial PFT interpretation. So this is her biphasic flow volume loop pattern that was noted on her initial PFTs prior to her undergoing the left main bronchus balloon dilation. So what you note here is, on the inspiratory limb, you'll see an end-inspiratory tail, and on the expiratory limb, you'll see an end-expiratory tail. We did end up doing repeat PFTs for this patient once the balloon dilation was completed, and they did look normal. So this is her PFTs after that, and as you can see, yes, there is some little bit of flattening on the inspiratory limb. However, she no longer has the end-inspiratory and the end-expiratory tails that were noted prior to her balloon dilation. Because this patient was pregnant at the time of our diagnosis, we could not initiate induction therapy with typical agents such as cyclophosphamide or rituximab, hence we initiated her on a combination of prednisone along with azathioprine. Once she completed her pregnancy, she did go on to maintenance therapy with rituximab. Another thing to note for her is that we did go ahead and schedule her for a repeat bronchoscopy for her right upper lobe bronchus dilation, however, this was unsuccessful. And most recently, she had a visit in May of this year, and it appears that she has a recurrence of her left main bronchus obstruction. So the flow volume loop is really important for all us pulmonologists. It's the equivalent of an EKG for a cardiologist, really. So why is it so important? Well, it's important because it tells you what the respiratory cycle looks like at different points. We all know that the bottom limb is the inspiratory limb, and the top limb is the exhalation limb. In patients with unilateral main stem bronchial obstruction, like our patient here with MPA, you can get a typical biphasic flow volume loop. So how does this really occur? Well, the normal lung predominates the early cycle of both the inspiratory cycle and the expiratory cycle. So that's why it appears normal. However, since the obstructed lung, which is the affected lung, is not ventilating appropriately, it's in fact ventilating very slowly, it ends up going and having a tail. So you'll see both an inspiratory tail and a both, along with that, an expiratory tail. It's really important that we as physicians are able to recognize this biphasic pattern. I think we fall into the trap of really just being able to identify six main patterns on flow volume, restriction, normal, obstruction, variable extrathoracic, variable intrathoracic, and fixed. So we often are not looking for this, and we often do not have many patients with this, hence I think it sometimes can be missed. It's important to be able to recognize this biphasic flow volume pattern because it suggests a unilateral main stem obstruction. And this can be caused by many different diseases, not only MPA, but things like endobronchial tumors, things like amyloidosis, sarcoidosis, post-transplant anastomosis that has granulation tissue around it. So it's really important to recognize this so that the patient can undergo determination of the underlying etiology. That can help us initiate therapy appropriately and on time, and it can also help us make sure that the patient gets the appropriate bronchial interventions if any are required on time. Thank you. Thank you very much. Do we have any questions? So one question I have is, do you see that there's utility in using sort of serial flow volume loops for monitoring disease progression in this patient? So that's a great question, and after her initial left main bronchus dilation, we did go ahead and use her flow volume loops as a target to determine if she had a recurrence of her left main bronchus occlusion. However, on her most recent visit, she ended up having a CAT scan of the chest intermittently with her ENT, and there was a reoccurrence of her left main bronchus obstruction without necessarily having it affecting the flow volume loop. So initially, although we felt that could be the way that we could go ahead and monitor this patient for recurrence of obstruction, in fact, it was not. And I think that has a lot to do with the fact that we have to keep in mind that the biphasic flow volume loop doesn't always occur if you have less than 25% obstruction, and sometimes if you have even more than 75% to 80% obstruction, you may not see it on a flow volume loop. So you may necessarily only catch those patients that have between the 25% to 80% obstruction. Okay. And how do you think earlier recognition of this biphasic loop would have affected the management in this particular case? Yeah, so the earliest she actually had the subglottic stenosis dilation was in 2016, and we saw her as a visit in 2021. So she's had multiple five years where she's gone undiagnosed without being on any treatment for her MPA. So that's a long time for her to come in with subsequent need for procedures. So I think that it is important to be able to recognize this early, because if you know the underlying etiology, you can start treatment very quickly. And we all know the MPA, both induction treatment and really the maintenance treatment is so long. So being able to recognize these patients early on is really important. Okay. Thank you very much. Yeah. Thank you. Okay. Do we have William Smith here? Okay. Welcome. Perfect. So I have a case talking about cardiac limitation and exercise due to ventricular compression of patient with pectus. We'll kind of talk a little bit more about pectus. Ironically, my wife is a pediatrician and knew profoundly more about me than this topic, so it's been a fun learning experience. They've definitely paved the way there, which has not always been the case. I'm Tyler Smith. I'm a current third-year pulmonary critical care fellow at Mayo Clinic in Rochester. I have no financial disclosures. So just brief review of objectives. We're going to talk about a case of severe pectus with exercise limitation. We'll review some of the physiologic changes you see with severe pectus, discuss how these might manifest on CPET and why we do CPETs, and then briefly review kind of standard treatment. So just for a bigger overview, pectus is the most common congenital chest wall deformity. Significant male predominance, 3 to 3 or 5 to 1, depending on what you're looking at for different literature reviews. Often asymptomatic but can be associated with chest pain, exercise limitation. And there were a ton of studies even in the last 10 years where they're trying to define are there any actual exercise limitations or is there some mechanical costochondritis and we shouldn't be doing any procedures on anyone with the assumption that these are largely aesthetic problems. So the way this was initially measured is there's the pectus severity previously called the Holler Index. That's a ratio of the maximum transverse diameter of the ribcage compared to the shortest AP diameter looking at the sternum to spine. And I'll illustrate that so you guys don't just have to follow my confusing words there. Normal should be under 2, severe is greater than 3.5. Corrective surgery is usually just greater than 3.25 or with a significant exercise limitation. I'm not really discussing the intermediate ones because those vary a lot based on different authors and almost everyone suggests not really doing an intervention until you're seeing greater than 3.5 or so. So this is actually our patient. So you can see the ratio of 3.82, so AP diameter in the closest window you can get just over 7.8 centimeters and across the chest just under 300 millimeters. So pretty significant compression and the tricky part I think to highlight for clinicians here is that these CT scans we're usually getting for other purposes and we're asking the patient to maximally inspire to the best degree that they can. So this is the best this will ever look for this patient. So I think maybe an exaggerated response for looking better at parenchyma but not well defining our cardiac structures. So the case is a 19-year-old male. He actually presented with sporadic squeezing chest pain, palpitations, and he showed up for cardiopulmonary exercise testing to evaluate should he undergo surgical repair, which is the typical practice at our institution. This is a CT scan. Again, the same view I showed but from the side you can actually see that his right ventricle is right up against the sternum. And again, this is during maximal inspiration. So I think we would be saying that, you know, it's pretty easy to believe that he's probably going to have some difficulty filling and expanding that chamber. So we sent him for a cardiopulmonary exercise test. Please excuse the busy slide. I'll highlight some findings on the next part. But what we really see is he had a really significantly reduced amount of work he could undertake. His VO2 mls per kg was significantly reduced to 65% of what we predict. And his stroke volume surrogates of VO2 per heartbeat also blunted at 70% predicted. Worth noting that our baseline interpretation comes off of the old Jones exercise data. But if you put this otherwise healthy now 20-year-old male in the friend registry, he comes out in the 10th percentile of exercise capacity. So a lot of the debate is, does this really represent a deconditioning or a cardiopulmonary limitation? And I'd argue that most 19-year-olds that are walking around and have left the bed in the last few months, it's probably hard to argue that deconditioning's gotten him this low. This is six of the nine plots we show. And it's just kind of, if you look at plot two, you can see the heart rate really takes off pretty aggressively after loaded exercise. We know our typical response, heart does the same as the lungs, which makes CPET a little easier, right? You get bigger tidal volumes. You get bigger stroke volumes. Then when you can't do that more, you augment your heart rate or respiratory rate. And he really has an abnormal heart rate response to exercise. Here's our flow volume loops showing that we do not have any of the problems from the last case. He's not really approaching his maximal flow volume loop. And just on the left, highlighting that we used the two-slopes method to determine the anaerobic threshold, which came out to just around 30% of his predicted VO2 max. So we'd say normal should be 40% or further. So I think that also speaks against deconditioning with an early anaerobic threshold in his case. So the take-home was that he had a severely reduced peak oxygen consumption and exercise capacity, an early AT, a really blunted O2 pulse, and an abnormal heart rate relationship. His ventilatory equivalents were borderline. So there was some discussion, is there any pulmonary limitation to this at all? Which is actually a big caveat in pectus cases. But he had no clear breathing limitation. He had adequate breathing reserve of pretty much 50%. And his CO2 blew down at peak exercise, as we'd expect. He never had a desaturation. So based on that, we felt comfortable saying there was not a significant pulmonary limitation in his case. When we talk about exercise limitation in pectus, it's tricky because some people say that there's the theory of deconditioning begets more deconditioning. So it hurts when I run, so I don't run, so I can't run as much. The big causes we've actually seen are cardiac limitation, ventilatory limitation, and chest pain. The thoughts about whether we should take these people under at least intermediate risk surgeries to fix these with a NUS procedure or something else we'll talk about comes down to are we actually helping these patients get any better, and are we doing a large thoracic procedure for deconditioning? They've done decent meta-analysis with Dr. Malik and actually a few other ones where they've looked at teenagers and children predominantly, because that's the population we do these procedures in, and have shown that across the board, it's predominantly a cardiac limitation exercise with a similar pattern that we saw on our side. Ventilatory limitations are actually impressively uncommon, and significant pulmonary restriction is not terribly common. So that would be to argue that baseline pulmonary function tests and lung volumes are probably not going to be a good enough indicator to screen this population. So the corrective procedure he underwent was the NUS procedure. This was actually developed out in Norfolk, Virginia at the Eastern Virginia Medical School. And what they essentially do is they'll tunnel into the right chemothorax, and they essentially thread a steel introducer behind the sternum and just flip it 180. It looks like it would be painful. I would imagine it is. We now do intercostal ablations of almost all nerves involved when they place this. But you'll see in figures A, B, C, and D on the left, those are actually the different ways to elevate the sternum. And so that gives us a much safer window to perform the procedure. And you can actually see this is from his surgical case. So this is a picture doing a VATS coming from the right across. To the top is the back of the sternum, and you can actually see the pericardium there. So they tunnel from right to left. They essentially make a hole between the pericardium and the sternum under direct visualization. Complications aren't common, but when they happen, it's in the territory of cardiac lacerations, which are not great to do to 19-year-olds who are still walking around and breathing. So this has been kind of slowly tailored with VATS being much more involved in any open procedures. So he had two bars placed, so once they make that hole, they essentially tunnel an introducer bar over it, flip it open, expand the chest diameter. The left is not an actual lateral X-ray. That was a reconstruction from his initial CT since he didn't have X-rays and he was referred to us. But on the right, you can see almost some immediate improvement with his AP diameter. And then again from the left side and right, you can see two bars kind of not entirely parallel with each other. And I think the highlight here, too, is you see bilateral pneumothoraces on the left. So we made one continuous pleural space of that procedure. He did get a pigtail that stayed in for a day or two and had complete re-expansion of the lung. Pneumothorax risk, and this is about 30%. So big conclusions is that contrary to what I expected, cardiac limitations are much more common than ventilatory constraints in this patient population. Exercise limitation usually reflects people with an adequate breathing reserve and an abnormal heart rate response. That's the pattern you're most likely going to see on CPET. And the thought is this really is a physical mechanical constraint on the right ventricle's ability to fill. So on the CT scan, we saw that it just kind of pinned right between the spine and the sternum and they're just not able to augment their stroke volume and they end up losing preload to the left side. The normal index should be under two, severe is greater than three and a half. And then just to recap that the NUS procedure is the most common minimally invasive surgical repair. And that's been around for close to 40 years now. All right. Hello, everyone. Thanks for coming. My name is Alex Van. I'm a pulmonary critical care fellow at NYU. I'll be presenting a case of drug-induced hemolysis and methemoglobinemia. I have nothing to disclose and I don't have a headshot, so I'm in the market. The objectives of this talk are to understand the risks of tefeniclin in patients with G6PD, deficiency as well as the associated risk of hemolytic anemia and methemoglobinemia and the management in those complicated cases. So our case involves a 23-year-old gentleman who had a known history of G6PD deficiency. He also had a history of Lyme disease and reported babesiosis, although as you'll see, all this history is a little bit murky, who presented to our emergency department with three days of dyspnea fatigue, some mild jaundice and exertional dyspnea. Eight months prior to presenting to us, he had actually been seen by an outside provider who had diagnosed him with chronic Lyme disease, as well as babesiosis, although titers for both were notably negative. And he was started on a prolonged course of antibiotics, so at that time was on a continuous months-long course of Bactrim, Etovaquan and Ivermectin. And then one week to presenting to us, he was also started on tefeniclin, which for those of you not treating a lot of malaria, it's a derivative of primoquine with a much longer half-life and in rare cases has been used to treat babesia, or at least has activity against it. So when our patient arrived to the ED, he was hypoxemic, ultimately placed on six liters with a sat that never got above kind of 88 to 90% for us. His exam was notable for scleral or icterus and maybe a little bit of cyanosis, but nothing too impressive. You'll see on his VBG down here that his methemoglobin level on co-oxymetry was 7%. Typically we expect a methemoglobin level of 15 to 20% before you really get profound cyanosis. His labs were also notable at that time, as you can see, for pretty significant hemolysis. He had a decreased haptoglobin, elevated bile. And if you look at his trend, as recently as several months prior, his hemoglobin was almost around 15 for a healthy 23-year-old and rapidly had dropped to about two-thirds of that. So it was kind of in the 10 to 11 range when he got to us. This is a representative picture of his blood, this is not his blood. So he was ultimately triaged to the MICU, and part of that was in the setting of kind of rapidly progressive neurologic symptoms. He became quite lethargic, seemed a little bit confused, was complaining of a pretty severe headache. At that time we got a ABG that demonstrated his oxyhemoglobin on co-oxymetry was only 78%, and his methemoglobin had risen at that point to almost 10%. He was initially treated with high-dose vitamin C, but after discussion with our hematology colleagues that was ultimately deferred due to risk of further oxidative stress. Along the same lines, methylene blue was not a viable treatment for this patient because of his known G6PD deficiency, so we opted to pursue exchange transfusion. He ultimately received eight units of PRBCs with rapid improvement in all of his markers of hemolysis, his mental status also improved, and his methemoglobin quickly went to zero. He ultimately was discharged home very well about a day and a half later. So I thought this was an interesting case because this patient had really a double hit. He had the G6PD deficiency that we know about, and then developed hemolytic anemia and what was trending towards a significant methemoglobin anemia as well. The drug he had received, tefenoquine, is a known cause of methemoglobin anemia, and that can happen in patients with and without G6PD deficiency, although more likely in those latter patients, as well as hemolytic anemia, particularly in patients with G6PD deficiency. And as I alluded to earlier, the terminal half-life of tefenoquine is 16 days, so it's used in the malaria world as a kind of once-a-week treatment. So once you give that drug, there's kind of no turning back, and certainly not something we would encourage in patients like him. The other kind of risk factor this patient had was being on chronic Bactrim, which also is a risk for hemolytic anemia in G6PD, although much less so. So just to quickly review for everyone, just because I'm sure we don't look at our biochemistry pathways all the time, G6PD, it's an X-linked disorder. It's actually the most common inherited enzymatic disorder in red blood cells in humans. Like 400 to 500 million people around the world have some degree of G6PD deficiency. It's part of the pentose pathway that generates NADPH, which reduces glutathione, and glutathione is able to reduce oxidative injury, particularly in red blood cells, which are most susceptible to those stresses. Methemoglobin, on the other hand, is an oxidized form of hemoglobin and does not bind oxygen when it is in that oxidized form. The first-line treatment for severe or symptomatic methemoglobinemia is typically methylene blue, but unfortunately methylene blue is contraindicated in G6PD deficiency. It is both ineffective, because it needs to be reduced in order to do its job, and it also puts you at risk for worsening oxidative stress, methemoglobinemia, and hemolysis. So you really can't use methylene blue in these cases. Ascorbic acid, for similar reasons, at high doses that you use to treat this, can also cause oxidative stress somewhat paradoxically. Other options are hyperbaric oxygen therapy, which we did not pursue, and then RBC transfusion or exchange, which we did. So I think, you know, the conclusions are fairly clear here. Don't give your patients stefanoquin when they have G6PD deficiency. You can end up with this unfortunate double hit of hemolysis and methemoglobinemia. And in cases of salvage therapy, red blood cell exchange transfusion is a very viable option. Okay. Thank you. Thanks, everyone. Any questions? Go ahead. Alex, fantastic job. I'm glad to have this division director. Okay. You did a great job. Two questions. Is the drug that was partly complicit here, is it dialyzable and should there have been thought for trying to dialyze that drug long? Yeah, so we did not really, you know, I think at the point we were putting in a dialysis catheter to do it, I think that the easier option is just to do the exchange transfusion to kind of directly address the cause. I mean, I think if you're, he's undergoing active hemolysis, I don't think that was, you know, in our view going to correct the problem, although it would correct the driver of the problem. In terms of the carboxyhemoglobin, we never really pursued that, frankly, and I'm not sure to what extent that could have been contributing to any of his symptomatology. We did not have anything in his history that would kind of suggest, you know, a etiology for that. So he was a non-smoker? Non-smoker. Okay. Yeah, going along with that, is there a risk of, with the drug having such a long half-life of after you sort of get the hemoglobin down, having it occur again because he still has the drug on board? Yeah, I think that's certainly a valid concern. You know, I think in all of these cases of G6PD deficiency-induced hemolysis, it is the old red blood cells that tend to lyse first because they have become kind of depleted of their, whatever amount of G6PD they have. So typically what you see is, despite the kind of very long half-life of some of these drugs, kind of a rapid period of hemolysis, and then the kind of younger red blood cells are actually able to kind of ride it out. So it was definitely something that, you know, we had him come back several days later as an outpatient to, you know, recheck all his levels and seemed to be pretty stable, not having any more active hemolysis at that point. Okay, great. Thank you very much. Sure. Thank you. All right, do we have Augusto Neto? No. Augusto Neto here? Okay. Timothy Yang? Or wait, this is out of order. Is Edward Christopatius here? All right. Do you mind going early? Do you have people who are going to come specifically for you? Okay. So we'll go ahead and get started with you then. Okay. So hello, everyone, and thank you for joining the Long Physiology Challenges Session. So my name is Edward. I'm one of the third year internal medicine residents in the Cleveland Clinic Fairview Hospital. And today I would like to present a case of use of invasive cardiopulmonary exercise tests in a post-COVID-19 fatigue case of a tired athlete. So, and here you can see the lesson objective for today's topic. So without further ado, in winter of 2021, a young male athlete presented to emergency department with very nonspecific symptoms that lasted for three days. Frontal headache, generalized body aches and weakness, and a high-grade fever. His workup was remarkable for positive COVID-19 test and his AKG showed right axis deviation. The reason why they did an AKG, it seems like the patient was slightly dyspneic and fatigued, but however, he did not report any chest pain. So, and the patient was recommended to improve hydration, use acetaminophen for pain. However, as you can see in his follow-up visit with his primary care physician, in four weeks, he was still symptomatic. He continued to experience dyspnea and fatigue. So because of ongoing symptoms, his PCP decided to repeat the AKG and it again showed the right axis deviation. And it launched the cascade of the cardiac evaluation. So as you can see, his 2D echo revealed a normal ejection fraction, high RCA takeoff and with mild ectasia. Subsequently, he had an MRI which revealed area of myocardial enhancement with normal cardiac markers. So following the course, the patient started an aspirin for the coronary ectasia. And what is important for the case, he was recommended to abstain from physical activity for three months due to suspected myocarditis. But as you can see, it did not improve his condition and actually he became depressed, short of breath, lightheaded and lightheadedness was precipitated by a minimum of physical activity. So eventually patient was recommended to undergo a cardiopulmonary exercise stress test. And here you can see the results. His O2 consumption was reduced at the peak of exercise as well as his O2 pulse which we can use as a surrogate for his stroke volume. Here in a plot two, you can see that his heart rate went up all the way which appropriately shown here. However, on the other hand, his VO2 heart rate did not reach the threshold. The same as in a plot three, you can also see that there is a decreased performance. So given the above results, he was started on the, he required some additional workup. He underwent pulmonary and physical rehabilitation which did not provide any improvement. He also had a DFT and a chest CT which did not show any abnormalities. And his cardiac MRI actually showed that he had a resolution of that focal area of enhancement. So because we still don't have an answer on why the patient has a persistent symptoms, it was decided to proceed with invasive cardiopulmonary stress test. So the patient was on a treadmill, A-line was inserted along with a pulmonary artery catheter. ABG and hemodynamics were recorded every minute during the exercise. So, and what is interesting here on a CPET portion, you can see that his O2 pulse and oxygen consumption actually improved. However, when we go to the hemodynamic portion, you can see that on a maximum of exercise, there are a couple of interesting details. Well, first of all, his RA pressure had barely elevated. It stayed at the level of three. His pulmonary artery pressure was appropriate for his exercise and his pulmonary capillary wedge pressure was low as well as his cardiac output. So you can also see on a graph with a central venous pressure that his RA at the maximum of exercises marked by the star that didn't really go up. And you can see that his wedge only doubled in amplitude. So, again, just to emphasize on how, why we labeled it as abnormal hemodynamic profile, his expected cardiac output was actually 22.3 liters. He was able to achieve only 16.6, which makes it about 74% of predicted cardiac output. So, eventually patient was recommended to wear compression stocking above the knee, improve hydration and exercises lower extremity muscles. In three months follow-up, patient finally sustained some improvement of his symptoms. And I know why the case was interesting to me. Well, this knee, as we know, was a major symptom, major comorbidity, which has a lot of differential diagnosis and it seems like in a post-COVID era, we now have another one, which is a long COVID syndrome, which we don't really know what is the pathophysiology behind it. We know that there are some reports that suggest that it can be due to autonomic dysfunction and adrenal insufficiency. And now we have this case of a young athlete with that kind of a hemodynamic profile. What do we know about the preload insufficiency? Well, let's see. So, this is just to emphasize how frequent is dyspnea in a post-COVID-19. And in 2016, Oldham with colleagues actually attempted to evaluate the preload limitation to exercise in their retrospective study on 619 patients. They discovered that preload insufficiency as a hemodynamic profile can lead to dyspnea. They also discovered that for some patients who received volume resuscitation with a normal saline, their dyspnea and exercise capacity actually improved. And as a result of the study, now we have the criteria for preload insufficiency that we can use in our clinical practice. And just for simplicity, I know it's a busy slide. I'm just gonna mention the criteria here. As you can see, in the case of our patient, he matched the criteria because his peak cardiac output was less than 80%. His right atrial pressure was three, and the criteria is actually less than 6.5. And his wedge was 11, and the maximum was only 12. So in conclusion, just the take-home messages. Invasive cardiopulmonary stress test is a very useful diagnostic tool that we can use for dyspnea of unknown origin. Preload insufficiency can be connected to the long-COVID syndrome, and can be potentially treated with intravascular volume expansion. And that's all, thank you. Thank you. Thank you very much. Any questions? So I think that this highlights how sort of the non-invasive cardiopulmonary exercise test can just sort of tell you that there's a cardiac limitation, but it doesn't tell you what about the cardiovascular system is actually causing the limitation. Did you see that the anaerobic threshold and lactate levels also sort of corresponded with sort of insufficient cardiac output? Thank you, just a very valid point. So I did not include the actual ABG data because it was all within normal limits. His lactate stayed within normal limits as well. So that was the discrepancy. Okay, all right, very good. Any other questions? Okay, we'll move on. Thank you. So now we'll... Good morning, everyone. Thanks for attending the lung physiology session. So I'd like to present a rare and intriguing case of combined dysuria and dyspnea. My name is Augusto Moronetto. I'm an internal medicine physician in central Montana and I have nothing to disclose. So what are the learning objectives? So we're going to talk about sulfohemoglobinemia as an entity and kind of go over the path of physiology and that leads to cyanosis and talk about possible treatment options. So the case is a patient that's a 46-year-old female with spasmodic risk for bipolar disorder with recurring UTIs that was dealing with the chronic dysuria and was taking a lot of over-the-counter phenazepiridine. And she started presenting some worsening shortness of breath for two weeks and noticed some skin changes and was feeling very fatigued. So she ended up going to the ER. When she went to the ER, during her exam, vital signs were essentially normal except for saturation with 80% of room air. On physical exam, she had some clear lungs, but she definitely had some perioral and peripheral cyanosis. So the ER doctor ordered some labs that, and when the blood was drawn, the nurse noticed that the blood was very, very dark. So that's what the, so that was the picture taken at that time. And essentially kidney function, hemoglobin levels, lactate, LFT, creatinine, everything was okay. Everything was normal. What got to our attention was when we got the ABG, you know, she had this SpO2 83%, PAO2 was fairly high, comparatively, 78, right? So if you just got to remember, for SpO2 90%, you're aiming at PAO2 around 60. So that was a little bit unexpected. And the coximeter end up noticing that metahemoglobin levels was fairly low, and there was an interference with suphohemoglobinemia. So we end up sending out the lab to check the levels of suphohemoglobinemia was very high. So patient end up being admitted for supportive treatment. It was offered, it was offered also different options of treatment, but she just didn't want to do it, and she remained in the hospital and eventually was discharged home on oxygen. So let's review a little bit of the pathophysiology of suphohemoglobinemia. So what happens with suphohemoglobinemia is that sulfur, so first you have the oxidation of the iron, forming ferric iron, and then the hemoglobin pretty much becomes nonfunctional. So you do have a little bit of functional anemia, and sulfur also is added to porphyrin, also another reversible change. What happens to the hemoglobin then? Well, you have some normal hemoglobin circulating, you have some affected hemoglobin. The normal hemoglobin is going to start unloading the oxygen easier. So it actually causes some right shift deviation of the oxygen dissociation curve, as you can see. So when I first started reading this paper and preparing, I was intrigued by the fact that there was some right shift deviation. So what happens in metahemoglobinemia, you have some left shift deviation, the presence of the metahemoglobin makes the normal hemoglobin attach to the oxygen, and it makes it harder to unload the oxygen to the tissue. And that's a different story what happens with the suphohemoglobinemia. In this case, the presence of suphohemoglobin makes the normal hemoglobin to deliver the oxygen and release the oxygen in a facilitated form. So it deviates to the right. And that explains a lot of things. So we're talking about this hemoglobinemia here, and the metahemoglobinemia is very well known. Suphohemoglobinemia, it's not as common, but the behavior is different. So the suphohemoglobinemia, patients tend to tolerate it better. They have less hypoxia comparatively, and they look less ill to the level of their oxygenation. So let's say they come in with SpO2 of 80%, but they don't feel as sick or they don't look as sick, because what actually happens is a right shift deviation of the curve, which is interesting. So that brings us to a little bit of a broad discussion of this hemoglobinemia. The three main ones that you want to walk out of here without having questions about. So we briefly touched base on suphohemoglobinemia. Also mentioned the metahemoglobinemia, and the carboxyhemoglobinemia also is a big one. So it's really important to step back a little bit and talk about pulse oximetry. So the pulse oximetry, it reads the wavelength, and the different type, these three different types of hemoglobins, they capture the wavelengths differently. So what we need to know is the carboxyhemoglobin, it really captures and behaves as oxhemoglobin. So if someone comes with carbon monoxide poisoning, what you should expect, well you're going to see normal pulse oximetry, SpO2 of 94%. Don't let yourself be fooled, because again, it's a very tricky behavior, the carbohemoglobin behaves as oxhemoglobin, right? So you're going to have normal. And the metahemoglobin, it's a mixed behavior, so you're going to have capture of different wavelengths and it behaves a little bit of like the oxyhemoglobin and also deoxyhemoglobin. So you're going to end up with SpO2 or around 80% on your pulse ox. On the other hand, the suphohemoglobin really behaves more like a deoxyhemoglobin. So you're going to have lower sets, but again, the PaO2 ends up being on the higher side as it causes a right shift deviation. So the other treatment option, as I said, for suphohemoglobin would be pretty much, as I said initially, you try the support of treatment, but patients may be a candidate for transfusion or exchange transfusion. In this case, my patient is not accepting the exchange transfusion and she did just fine on oxygen. So you should offer that when you have tissue injury. So in conclusion, it's important to acknowledge that this entity called suphohemoglobinemia that can cause cyanosis and patients are going to look proportionally less sick by the degree of the hypoxia. It's important also to remember that some co-oximeters, they're going to report interference, but if you don't go after that, it's not necessarily automatically reported in your electronic medical record. So it can lead to a near miss event. In our case, the RT was very clever and he actually noticed that and he actually told the team that this could be happening and ended up being a lab sent out and we checked the suphohemoglobin level, it was high. So yes. Thank you very much. Thank you. Any questions? So, very good. One question, as you mentioned, it was a send out lab, so it must have taken some time for that result to come back. How much anxiety was there in waiting, because you had a sort of preliminary diagnosis, but you didn't know for sure that that was correct and so what was it like to manage the patient? So I think the key points is, common things being common, someone is cyanotic, you want to rule out your P, you want to rule out any parenchymal disease, you want to rule out your cardiac shunt, so the echo was reassuring, the CT was reassuring, everything was reassuring. This history was very leading, I guess, the patient was taking phenazepiridine, which potentially can cause both metahemoglobinemia and also suphohemoglobinemia. And so we were kind of, we didn't really anchor, but I think we ruled out the most serious stuff. And patient was feeling fine, and I think what led us is like, okay, let's forget about the testing, let's focus on the patient, how does patient look? Look super sick? You know, is he in respiratory distress? No, the patient was comfortable. So I think that kind of helped us calm down. Okay. All right. Thank you very much. Thank you. Great. Thanks everyone. Good morning. My name is Timothy Yang. I'm a chief medical resident at Kaiser Permanente in Oakland, California, and I have no financial disclosures. So I'm presenting a case of hypoxia and recurrent hemolysis in the setting of amyl nitrate use. So getting into it, we have a 68-year-old man who presented to the emergency room due to hypoxia during a six-minute walk test in clinic. He reported cough but minimal dyspnea despite an initial SpO2 of 81% on room air. In the emergency room, he was placed on CPAP of 10 centimeters of water with 100% FiO2, and his SpO2 improved from 81% to 88% to 90%, and he was admitted to the ICU for closer monitoring given undifferentiated hypoxia. His past medical history was notable for obesity, obstructive sleep apnea. He was a former smoker of 30 pack years but reported quitting 24 years prior, and he had four to five alcoholic drinks a day but did not disclose any other substance use in his other history was unremarkable. His objective data, his exam was only notable for fine bibasilar crackles in the bilateral lower lung fields. His ABG on a 100% FiO2 CPAP of 10, his SpO2 was 88%, revealed that he had a FiO2 of 472. His hemoglobin was 13.6 with a macrocytosis and normal platelets. His imaging revealed a trans-thoracic echocardiogram that was normal and a CT chest pulmonary angiogram which was negative for acute pulmonary embolism but did show subplural reticulations and garniculopasities with small subplural cysts and generalized traction bronchiectasis. You can see the subplural cysts here. His additional labs were notable for a progressive anemia as well as markedly elevated reticulocytosis and evidence of hemolytic anemia. His direct Coombs test was negative. His flow cytometry for PNH was negative. His G6 PD activity was normal, and he had normal vitamin B12 and vitamin B9. So just summarizing the case, we have a 68-year-old man who presented with hemolytic anemia and hypoxia with a notable SpO2-PaO2 mismatch and evidence of pulmonary fibrosis. This differential diagnosis here for low SpO2 but a high PaO2 brings up abnormal testing, so abnormal pulse oximetry due to dark skin, though typically overestimates SpO2 or nail polish, and then discotechemoglobinemia is either acquired due to sulfhemoglobinemia or methemoglobinemia or hereditary hemoglobinopathies, including inherited methemoglobinemia as well as other hemoglobinopathies. Visiting and looking at that differential, we got some additional history on hospital day two. The patient admitted to recreational use of four to six 5-milliliter vials of amyl nitrite poppers three times a week, and his last use was one day prior to admission. He had further chart review revealed that he had actually reported similar use to his pulmonologist 15 years prior, and one year prior he had seen a hematologist for an episode of hemolytic anemia. That resolved spontaneously, and no hypoxia was noted at that time. We also sent a co-oximetry on hospital day two on FaO2 70% as SpO2 was 88%. That again demonstrated a significant mismatch between the PaO2 and the SpO2. The methemoglobin level on this co-ox was normal. We were suspecting the diagnosis of methemoglobinemia and sent out a direct spectrophotometry panel on hospital day three, and that eventually returned with a normal methemoglobin level as well as a normal sulfhemoglobin level, and he had inherited a hemoglobinopathy panel, including G6PD deficiency testing. That was negative. Just taking a moment to review the exposures that can lead to acquired dyshemoglobinemias, there's significant overlap between the exposures that lead to both methemoglobin and sulfhemoglobin, but as you can see, nitrites, nitrates in what this patient was using only lead to methemoglobin. So our patient was diagnosed with methemoglobinemia and hemoligninemia acquired from amyl nitrate toxicity, and you may be scratching your head as to how we arrived at this diagnosis with normal co-oximetry, normal send-out panel, and we really looked at the differential diagnosis and were able to rule out the other things on the list. Additionally, you know, he had some key features that were consistent with this diagnosis, the hemolysis, the SpO2, PaO2 mismatch, and the toxic exposure consistent with methemoglobinemia. Looking a bit at his timeline, you know, he last used the methemoglobin, or he last used the amyl nitrates one day prior to admission. There was a bit of a delay in our testing, so we tested him with co-oximetry in hospital day two and the send-out panel in hospital day three, which likely explains the fact that these were normal with delayed sampling. So what are poppers? These are amyl nitrate or butyl nitrate inhaled substances used to induce smooth muscle relaxation, basal dilation, euphoria, and patients using these substances may lack awareness of their detrimental effects. Amyl nitrates exert their toxic effects on red blood cells via oxidation of hemoglobin from the ferrous to the ferric state. This results in hemoglobin that irreversibly binds oxygen and conformationally altered hemoglobin that can lead to hemolysis. This is more pronounced in patients that have G6PD deficiency. And as Dr. Nitto was explaining to us, you know, the detection of methemoglobinemia can be challenging on routine pulse oximetry, and this is because methemoglobin absorbs light at both 660 nanometers as well as 940 nanometers, making it difficult for the oximeter to discern between deoxy and oxyhemoglobin. Co-oximeters measure more wavelengths and can make that distinction. However, the most accurate method of detection is direct spectrophotometry. And as we learned earlier, you know, methemoglobinemia can spontaneously resolve within 36 hours, which may lead to that sampling error if tested too late. The treatment of acquired methemoglobinemia is, of course, with cessation of the offending agent. You can treat with methylene blue if the methemoglobin level is high enough. However, you know, methemoglobin may be worsened by methylene blue at high doses, and methylene blue, when administered in the setting of hemolysis, can worsen the hemolysis, especially in the setting of G6PD deficiency. So you really need to make sure that you're not going to cause those side effects. If hemolysis and methemoglobinemia is present, you can consider some of the salvage therapies presented earlier, including ascorbic acid. So in conclusion, this patient was managed conservatively due to the clinical stability and the concomitant hemolysis. Although his SpO2-PO2 mismatch resolved by the time of discharge, subsequent ABGs revealed elevated AA gradient, and this was attributed to the discovered pulmonary fibrosis. And in pulmonary follow-up, he's had additional workup that revealed findings concerning for inhalation-related pulmonary fibrosis. These are my co-authors, and thank you. I'll take any questions. Thank you.