was unable to make it for his seat questions, so I'll be delivering those this morning. These are his conflicts of interest he wanted to disclose for the content that's in his questions. I don't have any. So let's get started. We have seven questions. All right, first one has to do with six-minute walks. A patient is referred to your PFT lab to undergo a six-minute walk for clinical evaluation of interstitial lung disease. They receive an exertional supplemental oxygen of four liters through nasal prongs, and the requisition states that the patient will be initiating a new therapy, and a repeat six-minute walk will be requested after two months to assess for a therapeutic response. Regarding the performance of a six-minute walk test in this setting, which of the following is true? A, two tests should be performed for the baseline assessment. B, the test should be performed without supplemental oxygen. C, no encouragement should be provided to the patient during the test. D, testing should be undertaken on a motorized treadmill rather than in a hallway. Which one of these statements is true? All right. All right, we have a good discussion point here. The correct answer is A, but there's a lot of different responses. So let's go over the details behind a six-minute walk test. Oh, and if it's any consolation, when, you know, this is Darcy's question, I got this wrong. So the six-minute walk test, I learned something from this dude, is a safe, simple, practical test, functional capacity. And it's responsive to various interventions, altered inspired gases, pharmacologic therapies. But it does correlate with outcomes, and which is why it's widely used to assess responses to interventions and treatments in a variety of diseases, including COPD and interstitial lung disease. So it demonstrates a ceiling effect in near-normal patients. And it's important to realize that, you know, the test itself, which is self-paced, is really the result of their walking distance. It doesn't really tell you why they may be limited. It's more of, this is the degree to what they're limited. So it's important to remember that when you order these tests. It's not a diagnostic test. It really monitors your functional ability. So while it shows excellent test, retest reliability, there's a learning effect. So two tests should always be performed initially when the six-minute walk test is used to assess change over time. That's why answer A is correct. So patients do better on their second go-around than their first. And you'd be misled if you just did your initial one and then waited two months and did the other one, because the improvement just might be the learned effect of the test itself. And there's data to suggest that that improvement, just on the retest, can be up to 30 meters. The test can be performed with or without supplemental oxygen, with or without encouragement. But the key is that as you do your six-minute walk tests, you standardize the process consistently. So you don't do it on a treadmill once and on an open circuit on the other. You don't do it with coaching on one and without on the next. You have to have it standardized. And Darcy's got a nice little table here that shows some of the variations in testing and their effects on the performance. So if folks walk in a hallway rather than a treadmill, they can do 20% better on the hallway than on the treadmill. Indoors versus outdoors makes a difference, as does whether the track is circular or straight. So I don't know about a lot of you guys. In my hospital, it's the hallway outside a clinic, back and forth. And if it's too short, OK. But the key is you just do it consistently each time. So here's a nice reference for some of the differences. And some more references if anybody wants to look in this a little further. All right, that's the first one. Second question, which of the following patients with COPD would be most appropriate to consider initiation of long-term nocturnal non-invasive ventilation, NIV? Which one of the following patients? A, the patient who's been discharged from the hospital after an acute exacerbation of COPD four weeks ago, currently with a PaCO2 of 52 and a pH of 7.36 and clinically stable. That's A. B, they're in the hospital recovering from an acute exacerbation, managed initially with NIV, but now ready for discharge. Their PaCO2 is now 62 and pH 7.34, and they're clinically improving. C, the patient who may be discharged from the hospital just two days ago, current pH 2 is 62, pH 7.31, and they're experiencing some slight worsening of shortness of breath. Or D, a patient who's from the hospital four weeks ago, current PaCO2 is 64, pH 7.36, and they're awaiting a polysomnogram because of some suspicions for a sleep disordered breathing, clinically stable. Which one of those patients would be most appropriate for long-term nocturnal non-invasive ventilation? All right, so the majority of you got this question correct, and let's go through why this is the correct choice. So this is a survival plot of non-invasive ventilation in patients with severe COPD who have stable hypercafnea. These patients clearly do better when they have non-invasive versus just oxygen alone. And the key here is that we're talking about stable hypercafnea, and that's why answer A was correct, is that not somebody who's slowly getting better, slowly getting worse, but they've reached a point of stability in their disease, and it's significant. So how do we define that? Well, first of all, the data, as Darcy points out, is limited, but it's been fairly consistent. So there's an increase in quality of life in six-minute walks. They're daytime awake. PCO2 is lower, these folks who use non-invasive at night. Dyspnea, admissions mortality is a little questionable. But we're talking about the stable COPD patients with severe disease defined as a PCO2 greater than 46, and without somebody who has some maybe alternative explanation for their hypercafnea, so some other obstructive sleep apnea or something else. And the whole goal is to normalize or lower the PCO2 and improve symptoms. So answer A was correct, is because this patient was in a stable state four weeks out and still had hypercafnea. B is incorrect, because the patient, while their PCO2 is plenty high, they're still recovering. And you wait a couple of weeks, that PCO2 may normalize, and they may not benefit from this. C is incorrect, because, well, it's just been two days, it's not long enough, and they're actually getting worse. So they're not in a stable state as it is. And D is incorrect, because the patient may have a confounding explanation for the hypercafnea. So wait for the polysomnogram. So nocturnal, non-invasive, stable COPD with hypercafnea. And here are Darcy's references. Okay, moving on to question three, preoperative risk assessment with CPET. So a 71-year-old female is referred for cardiopulmonary exercise testing in the setting of lung cancer and potential surgery. She was recently diagnosed with a 2-centimeter right upper lobe lesion, and after a thorough staging investigation, is being considered for a surgical resection of the right upper lobe. She has an established diagnosis of COPD, and her management is optimal. BMI is 23 with normal vital signs, breast sounds are reduced, and no focal lung findings. And the remainder of her physical exam is normal, electrocardiogram is normal. These are her pulmonary function tests. The shaded columns represent the patient, an FEV1 of 1.99, which is 56% predicted, FEV1 of 1.28, which is 51% predicted, ratios low, total lung capacity of 4.95, which is a little low, but within normal range, and her residual volume is a little high at 2.96, which is 136. And this is really no change after bronchodilators. So these are her PFTs. This is her CPET studies. So let me go through this here. There's a lot of information here. We have the workload at the top, her end exercise is 74 watts, which is predicted maximum was 107, so 69% predicted. Her VO2, weight-adjusted and regular, is about 98, 96% predicted. Her hematopoietic threshold is 0.98. Her minute ventilation is 56 liters, predicted was 49. Her SATs stayed stable and good throughout the test. Her heart rate nearly doubled to 142, with a peak predicted heart rate of 164. Oxygen pulse doubled around to 10.4, which is 90% predicted. Her blood pressure went up a little bit, as did her dyspnea scores. That's the result of her CPET. And so the question is, based on the information provided, what is your recommendation regarding lung resection? A, she should undergo a stair climb or shuttle walk test. B, she should undergo a radionuclide perfusion scan to measure the fraction of total perfusion for the resected lung, that right upper lobe they're targeting. C, she should just go to a lobectomy. D, she's not a surgical candidate because of her impaired pulmonary function test and functional status. What is the correct answer here? All right, so two-thirds of you selected the correct answer. She's ready to go for a lobectomy. All right, so let's go through the data and why this is the correct one. So this patient, granted, has COPD, demonstrates a normal aerobic capacity. Her VO2 was spot on what was predicted for her age. And so this is really the gold standard for assessing somebody preoperatively. So she is at relatively low risk and able to undergo a lobectomy. That's why choice C is correct and choice D is incorrect. Because her maximal VO2 from CPET exceeded 20 mils, there's no need, there's no added value to undergo a stair climb or shuttle walk test or a lung perfusion scan. That's why the other answers are incorrect. Darcy's got a nice little clinical algorithm you can follow for assessing these patients. The font's a little small, but on the far left is, you know, these patients who have a negative cardiac evaluation. Then you do a predicted postoperative FEV1 and diffusion. And if it's real low, less than 30%, these patients, if you're still going to consider surgery, they probably should undergo a CPET study. If it's real good, over 60%, they're pretty low risk and you can just go ahead. And if it's between 30 and 60, this is where you can go and maybe a stair climb or a shuttle walk test might give you enough information and identify those folks who you are low risk. And if it's a little sketchy, then they might need to go on to get a CPET. If you do get a CPET, and these are the numbers that I try to remember in my head is, if your VO2 is greater than 20, you're probably low risk. If it's less than 10, you're high risk, and then in between, you're moderate. So it's a nice little algorithm that you can use if you're going to use CPET, stair climbs, or shuttle walk tests when you're evaluating these patients for surgery. And these are his references for this algorithm and question. Okay, question number four. This is regarding triple therapy versus double therapy in symptomatic moderate to severe COPD and a history of frequent or severe acute exacerbations of COPD. Which of the following statements is true? Okay, I overheard Sandy just giving this lecture. So let's see how we do. Question A, or option A, labalama therapy improves lung function and health-related quality of life and reduces side effects compared to triple therapy. Option B, triple therapy improves lung function and health-related quality of life and reduces acute exacerbations and mortality compared to double therapy with a labalama. Option three, or option three, excuse me, triple therapy and double therapy, dual therapy, similarly improve lung function and reduce exacerbations, but the triple therapy improves health-related quality of life compared to labalama. Where should the fourth statement? The benefits of triple therapy and labalama therapy are similar, but the risk of pneumonia is increased with the triple therapy. Which of the following, which of those four statements is true? All right, great. So yeah. So Sandy, that's immediate feedback. Your lecture was extremely effective. Eighty-five percent of the people got this question correct. Let's go through it in a little detail. This will be quick review, I think. Symptomatic patients with moderate to severe COPD and a history of frequent exacerbations, the triple therapy improves lung function, symptoms, health status, and reduces exacerbations and mortality compared to dual therapy. And frequent is defined as more than two exacerbations in the past year, and severe is anything that results in a hospitalization. So this is a forest plot of some of the data behind some of this on the relationship between COPD and pneumonia. And these are some risk factors for pneumonia. And you can see down toward the bottom is the inhaled corticosteroid use. Yes, it does increase your risk, but not anywhere near some of these other variables that play a bigger role in developing risks for pneumonia. And this is, again, some data regarding the benefits of the triple therapy versus dual therapy for moderate and severe with forest plots, those who want to dive into the details. And, again, some more literature and some references to the impact and ethos trials that Sandy just recently covered. And more references. All right, moving on. This is the last one for Darcy. So in a 69-year-old with COPD on triple therapy with recurrent exacerbations, which of the following would make her most suitable for starting riflumilast? Symptoms of chronic bronchitis. At least one hospitalization for an exacerbation in the previous year, and an FEV1 less than 50%. Or is it a former smoker with multiple exacerbations in the previous year, and an FEV1 less than 80%? Or is it somebody with recurrent pneumonia or oropharyngeal candidiasis, multiple exacerbations in the previous year, and a blood EO count less than 100? Or is it somebody with a COPD score greater than 10, a CAT score, excuse me, or greater, multiple exacerbations in the previous year, and a blood EO count greater than 100? Which one would be most suitable for starting riflumilast? ♪♪ All right, 79% got the correct answer. So this is about various oral medications and therapies for COPD. Riflumilast, as Sandy covered, a once-daily oral medication reduces the frequency in moderate and severe exacerbations treated with systemic corticosteroids in patients with chronic bronchitis, severe to very severe COPD, and a history of exacerbations. That's why answer A is correct. Azithromycin may be considered in patients with moderate to severe COPD to reduce exacerbation rates in former smokers. Withdrawal of inhaled corticosteroids can be considered if there are repeated bouts of pneumonia or other considerable side effects develop. Choice C is incorrect. And the blood EO count can help identify patients who may have a greater likelihood of benefiting in response to an inhaled corticosteroid. So symptomatic patients with a CAT score over 10, further exacerbations while using a Lavalama, and a blood EO count greater than 100 or escalation to a triple therapy may be considered. That's why choice D is incorrect. Again, I think, Sandy, you had a very similar table in your presentation on CAT scores and risks and treatment therapies as starting points for your patients, and some references for oral therapy and the management of COPD. Okay, these last two questions are mine. This is a 56-year-old patient. He's referred to you by his primary care physician for a thoracentesis. He presented three weeks ago with mild but progressive dyspnea and exertion, no history of chest pain or symptoms suggesting some pulmonary infection. He's a lifelong non-smoker and no occupational exposures, not taking any medications, and his evaluation reveals a normal EKG echo and with a normal left and right ventricular function. Results of laboratory studies include a normal hemogram, thyroid function tests, and no elevation of an ANA. On your exam, he's comfortable, normal vital signs. Cardiac is normal, but there's significant edema in his lower extremities up to the thighs. Left-sided ultrasound thoracentesis yields a 400 milliliters of slightly milky fluid, scant red blood cells microscopically. The cytology is negative. Gram stain and cultures were negative, and the laboratory analysis on the fluid is on the right in the table, and it reveals 2,700 white cells, of which 62 percent are lymphocytes. Glucose is 80. Total cholesterol is 30. Triglycerides are 85, albumin 2.9, and an LDH of 66, whereas serum is 90. So the patient had some modest relief of the dyspnea following the procedure, but it returned three weeks later, and a follow-up chest X-ray revealed some reaccumulation of the fluid. So based on these findings, which of the following abnormalities in this patient is this patient most likely to develop in the future? So you have to know the diagnosis at this point and identify what other findings and abnormalities could develop and are known to be associated with this diagnosis. Is it A, emphysema? B, this patient's more likely to develop non-small-cell lung cancer, or will they develop bronchiectasis? Or is it higher risk for malignant mesothelioma? Which are they most likely to develop in the future? All right, well done. So this patient has yellow-nail syndrome, and of the choices, this is the strongest associated with the future development of bronchiectasis. So yellow-nail syndrome is a pretty quirky disease. We don't really know too much about it, but it's been associated with pleural effusion, lymphedema, as in this patient, yellow nails, chronic sinusitis, and bronchiectasis. Those are the diseases that are associated with yellow-nail syndrome. It's pretty rare, likely sporadic, maybe a genetic predisposition, but there really is no specific test or finding to make the diagnosis. It's really a clinical diagnosis with exclusion of other causes. The pathophysiology is speculative, but there may be the role of, in terms of lymphatic drainage, and people have done lymphograms trying to identify where the blockage or slow inflow may be that results in the lower extremity edema. It's tricky management. We really don't have, it's rare enough that we don't have any good clinical trials to tell us what therapies work better than others. So you're trying to reduce symptoms and try what you can, whether it's possibly with diuretics or other things. And the pleurofusions can be, if you guys are taking care of patients like this, you know they can be particularly tricky. Some people have even tried pleurodesis to reduce them because they can be so stubbornly symptomatic. So quirky disease, could show up on the boards. You know, if they show you a photo of somebody's fingernails, it's probably yellow-nail syndrome. Or it could be mechanic's hands. They want you to see the hands, maybe. All right, last question. This is a stats question. Oh, yeah, growling. Happens to be my favorite. A 70-year-old self-refers to you regarding potential risks of their newly prescribed treatment, which is a factor Xa inhibitor, for their atrial fibrillation. They had learned of potential development of interstitial lung disease while taking these medications and are concerned this would happen to them. This is a very well-informed patient. In reviewing the most recent retrospective cohort study of a very large population, the authors reported, did report a higher incidence, incident risk of ILD among those patients taking a factor X inhibitor when compared to taking warfarin. And that was a 0.29 versus 0.17 per 100 patient years with a hazard ratio of 1.54. Dabigatran, which is a direct thrombin inhibitor, had an insignificant difference from warfarin. So the authors then said, okay, let's, we're going to use a, what's called a propensity scored stabilized weighting. You don't know how they, don't worry about knowing how to do that. But they do this to help balance out other variables that could confound the question of the role of factor Xa inhibitors in developing ILD. So all the other potential confounding things to try to balance those out and just zero in on these medications. And when compared to warfarin, a 0.29 versus 0.17 per 100 patient years with a hazard ratio of 1.54. So on the far right in the blue font, there were 64,000 people who got the factor Xa inhibitor, 22,000 who got dabigatran, and about 19,000 who got warfarin. And then you can see the incident risk over, what, seven and a half years of those patients who, cumulative incidents of who developed interstitial lung disease. Okay, so the question, the stats question related to this is, which of the following statements is true? A, in the first year of this study, the number of patients developing ILD was the 64,000 times the hazard ratio equaled 187. Is that statement correct? Or is it B, the relative risk of developing an interstitial lung disease while on a factor Xa inhibitor compared to warfarin was the hazard ratio of 0.29 divided by the hazard ratio of 0.17 or 1.7? Is that the correct answer? Or C, the odds ratio of developing an ILD while on a factor Xa compared to warfarin is the 0.9 divided by the 0.17 or 1.7? Or is the correct statement D, in this study the hazard ratio is not the same as the relative risk or odds ratio? Which of these statements is correct? All right, let me see if I can scroll that up. There we go. So, yes, 44. Have you got the correct answer? And let's go through this. So, this is a real study. This is a large cohort of patients. And there is an increased chance of adverse reaction as they present the data as a hazard ratio. They present it as a had ratio rather than a relative risk or odds ratio. But they're all kind of similar statistical stools, statistical tools that can help you assess probabilities of events. Okay, so what are the differences? So, unlike odds ratios and relative risks, hazard ratios are probability, actually, let me back up. Odds ratios and relative risks are probabilities at a specific point in time. What's the probability at nine months, at two years, at four years? It's a very time-specific point. Whereas hazard ratios are time-to-event probabilities and account for developing an event at multiple points over a study period, at the very beginning, at the end, in the middle. And so, choice D is correct. It gives you a little bit more information. And it's not the same as an odds ratio or relative risk. So, this feature of hazard ratios allows better comparisons between groups and reduces the impact of various biases that can develop when subjects drop out early or can't complete the study as planned. They also factor in the impact of developing the event early in the time period or something real late. And you can see in this study with the graph above, based on the, here, there may be more of a concern later in the course of Factor Xa treatment, out there six, seven years, than early. And the hazard ratio takes that into account. So, calculating the incidence of interstitial lung disease at one year, which was the first option, can't really be done from data, from the hazard ratio data. And that's one of the reasons that that answer is incorrect. And the same applies to the odds ratio. So, back to the point of, for point-in-time measures of probability, odds ratios and relative risks provide some guidance, but in different ways. Because these things can get, can be chosen by statisticians and researchers to present probability of events, but they do so in different ways. Odds ratios are simply the odds of an event occurring in the intervention group divided by the odds of the event in the control group. But neither odds ratios or relative risks can be inferred from data from hazard ratios. So, I've got my favorite two-by-two table up there, treatments and controls, events and no events, and how you go about calculating the odds ratios and how you go about calculating relative risk. Hazard ratios are much more complicated in doing so. But this is math that I doubt they would ask you in detail, but it's possible they might hint at the differences. I think the key points here is that hazard ratios are time to event statistics that assess the possibility of developing event over a period of time, and that may reduce the biases of data collection and ascertainment. Both odds ratios and relative risks assess the possibility at a very specific point in time, okay? It's kind of like there's a parallel, survival and mortality. Mortality data has to do with a rate at a very, very specific point in time. Survival tells you how that is a time to event statistic and gives you a bit more information. So if you think about it that way, I think it'll be helpful. All right. My time is up, and that is our last question. So thank you. Thank you.

pulmonary diseases

COPD management

lung function tests

six-minute walk test

nocturnal ventilation

preoperative risk assessment

hazard ratios