Session 2 – Advanced Pulmonary Sarcoidosis – The Royal Brompton & Harefield Hospitals and SarcoidosisUK 2022 Sarcoidosis Patient Day

Transcript 

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Dr. Kouranos: Although I am a speaker in the next session, I would like to briefly introduce Dr. Felix Chua, who I have the privilege to work with. Felix is one of the most experienced clinicians that I’ve ever met, and has more than 20 years experience in respiratory medicine, particularly, ILD and sarcoidosis. Thank you, Felix, for chairing this session and I will pass this over to you.

Dr. Felix Chua: It was completely unnecessary, Vasilis. Thank you very much. I could say the same about you too, and I shall in a second. So, session two is entitled, advanced pulmonary sarcoidosis. This is a very important session. But firstly, good morning, everybody. And thank you to Vasilis, Professor Wells, and of course, SarcoidosisUK for staging this follow up to what was a highly successful inaugural meeting event last year. This second session is going to cover a very key aspect of sarcoid care, which is basically investigating and treating pulmonary sarcoidosis that has either progressed or has given rise to complications and today’s complication of interest is pulmonary hypertension.

And for this session, we have two speakers. So, Dr. Kouranos will be the first speaker and Vasilis needs no introduction. He has a major interest in sarcoidosis and he provides his expertise both in the general sarcoid service which is predominantly based on lung disease sarcoidosis. But he also takes part and is a major important figure in the cardiac sarcoid service.

The second speaker is Dr. Laura Price who is the respiratory physician here at the Royal Brompton Hospital. Her area of expertise is pulmonary hypertension related not just to sarcoidosis, but to a variety of chronic or long-term pulmonary conditions. And I have a co-chair today who is Mr. John Devine. And I think before we come to the speakers, Mr. Devine is going to show us a short video to kick start things. I just wanted to say that I’ve had a text from Dr. Price. She’s giving a talk at the same time. I think it’s ongoing on another Zoom conference, so she’s going to join us at 12 noon sharp or just shortly afterwards. If there is a gap then we’ll take a couple of questions between Dr. Kouranos’ talk and Dr. Price’s talk but we’ll make do. So, let’s start with Mr. Devine’s video. So, Mr. Devine, over to you.

John: Hi, I am John Devine. I am a patient with the Brompton. I’ve been there for the last five and a half years. I was diagnosed with sarcoidosis 18 years ago. I was working out and I went from being very active and running and stopped playing tennis and cycling and living a normal life to — well, still living a very good life, to be honest with you, for the last 18 years and enjoying my work and teaching and bringing up my son and living a largely full life. Yeah, life has been pretty good. But it’s definitely taken a bit of an edge off some things. You know, I can’t exercise. So, that’s been the main one, you know. And it takes a bit of energy off you and I do over the years occasionally get little sort of flare up sort of sights and brain foggy things.

And then the other big issue for me has then been moving on to drugs. So, I ended up at the Brompton, thankfully, five and a half years ago, because I knew things weren’t right even though I had been told in various ways it’s stable or burned out. And I’ve had a bad infection. I got to the Brompton and they diagnosed, no, you’re right, it isn’t right. It is inflamed, your lungs are inflamed, we need to damp down the inflammation, which they’re very good at to make sure that you don’t get any more scarring and to maximize your lung function. The main symptoms at that point were just not being able to, I could still walk for two-three hours quite happily. But you know, it just felt a bit more — everything felt a bit more tiring. So, I’ve been on drugs since then, methotrexate and steroids which has stabilized everything, as far as we know, in terms of lung function, in terms of scans, which is great, that has given its own issues. There’s no doubt about it, which I’ve been on — The main one for me has been more chest infections because of the immunosuppressant drugs, which just adds another thing into the mix. And as you know, very difficult sometimes to know what’s going on. Is it a little flare up with a sarcoid? Is it the infections? Is it side effects of the drugs that you’re on? And it’s hard to distinguish between them. In my case, I think quite often it wasn’t sarcoid, it was actually a chest infection. I was working with a lot of young people.

Coronavirus comes two years ago and it was unfortunate for me particularly because I was at that point at the worst infection I’d had in 18 years. I’m just getting over it but I wasn’t great. Nothing to do with the sarcoid, actually, but to do with the drugs, I think so. And that last two years have been tricky. It adds an extra strain and extra worry on top of the condition that’s already not great. So, you can’t pretend, you know, great, I’ve got sarcoidosis. But on the other hand, I wouldn’t say that it’s wrecked enough, and I’ve lived a good life the last 18 years. I’ve still had a good time, more difficult than it could have been and more trying times, no doubt about it.

Dr. Chua: Vasilis, I think that’s the end of the video. Would you please start your talk? Thank you.

Dr. Kouranos: Thanks. Let me share my screen. Thank you, John, for the introduction and Felix as well. I must say it’s very touching to see patients describing their experience. And we unfortunately do not have much time when we meet to discuss every single aspect of their condition, although we would like to hear more and more from them. I’m glad that we have moved from this picture and we are gradually getting back to normality. And I hope that next time, we will be able to speak to you face to face and be able to have a symposium only with patience for the first time.

My topic is about advanced pulmonary sarcoidosis, and I’ll just mention some of the epidemiological data to understand what we’re talking about. And as you know, the incidence of sarcoidosis is quite low. So, it’s a rather rare disease with five to 40 cases among 100,000 patients. The age peak is between 25 to 45 years old in both genders, although it has been described that there is a second peak in women about 50 years old. And that by its own illustrates how difficult things can be because this is in the more productive age of its individual. Sarcoidosis in black Americans is more prevalent than white Americans, as the study has shown and actually the black population tends to have more extra pulmonary involvement. It is interesting that the Japanese population has far more frequent ocular and cardiac involvement suggesting that there is a background genetic predisposition for the sarcoidosis patients.

What is really challenging for all the physicians working in sarcoidosis is the heterogeneity in variability at initial presentation, disease evolution and outcome. So, we have seen a number of patients that had been diagnosed with sarcoidosis. Incidentally, they went for a chest x-ray, which revealed enlarged lymph nodes, but the number of others that presented with systemic disease activity feeling quite fatigued, and have a number of symptoms. It is common among most of the patients that they have pulmonary involvement, and that’s why the respiratory physicians are mostly responsible for them. Looking at the evolution, we have seen also many patients that have spontaneous remission but there is a small group of patients that developed pulmonary or even extra pulmonary disease. So, it is appropriate to develop an accurate monitoring for them. The outcome is usually good, but respiratory failure and cardiac involvement are usually the cause of death among the sarcoidosis population, while pulmonary hypertension is considered to be an independent predictor of mortality.

What I have heard in the beginning from the sarcoidosisUK video, what I wanted to emphasize on this one is that actually it takes a long, long time for the patients to get diagnosed. And originally I didn’t believe that; how is that possible? But actually, there is even a study that has been performed that shows that the diagnosis in half of the patients takes more than three months. And as you can see, if we look at the fibrotic disease, it takes more than six months in more than half of the population. So, it’s actually very late, the diagnosis tends to be late. And that’s why sessions or events like this ones are important to raise awareness.

We know that the reduction in life expectancy among the sarcoidosis population is largely measured around seven to 8%. And we also know that it’s about 30% of the sarcoidosis patients have major organ involvement, which we will hear a lot about today. So, it means that if you make the calculation, it’s about a quarter of the sarcoidosis, patients with major organ involvement will have a reduction in the life expectancy. So, although this is a condition that is considered to be overall benign, with very low mortality rate as a whole, there are patients that actually are at higher risk, and this needs to be acknowledged from government authorities as well.

As I mentioned before, I’m privileged to work with Athol who has developed a simple algorithm in order to convince both doctors and patients to follow a very logical approach in their treatment. And this is where the major organ involvement comes in. This has been clearly described in our British Thoracic Society clinical statement on pulmonary sarcoidosis, as well as other guidelines that have come up since then, that Simon and Anjali very well described. It’s the danger from the disease that is our primary concern. And this is mainly due to major organ involvement like fibrotic lung disease, or cardiac involvement, or even neurological involvement. And unacceptable loss of quality of life is our parallel or even second concern. These two issues could overlap, but they’re not definitely synonymous. So, we always need to be mindful of both of them. In both occasions, spacing should be engaging in the decision making regarding the treatment, but if it becomes apparent that danger from the disease would require sarcoidosis expertise from the doctor to drive the patient safely in his disease journey.

How are we going to identify patients at higher risk? How are we going to identify patients with active or major organ involvement? So, we look at three things. One is symptoms and we are very careful in trying to get everything from the patient with regards to their functional impairment, or symptoms that are really important, such as syncope. And we try to stage their condition using functional tests, lung function tests primarily as far as the lung is concerned and imaging modalities. The third thing which has become the theme of the last few years is observation of the disease behavior. And you may know that Athol Wells has been a driver in assessing the disease behavior across ILD and sarcoidosis, and being the main patient behind the progressive fibrotic phenotype which has been nowadays identified. So, we want to understand if the patient has advanced disease, is this progressing or is this actually stable and dormant?

I will cover the pulmonary fibrosis aspect, as well as the advanced pulmonary involvement and Laura Price will come second about the pulmonary hypertension which is equally important.

So, with regards to pulmonary disease, again, we’re emphasizing on evaluating symptoms, lung function tests and imaging as well as disease behavior. And symptoms could be a large list of questionnaires, including the MRC questionnaire, as well as others, but also it can be tests including a six-minute walking test that is a very easy test providing us with a lot of information such as the saturation when walking. In patients who have persistent symptoms, we may even went on to a cardiopulmonary exercise test in order to simulate what is happening in their daily life especially with regards to exertion. From an imaging point of view, we have traditionally the chest x-rays, but the CT scan is far more detailed and offers us more information. I will show you later on what I mean.

Although this is quite complex and carries a lot of medical information, I just want to touch on the fact that this is the only staging system that currently exists, has been published by our group and actually divided the places between high and low risk. And CPI is a composite physiological index, it’s a number that is created through an equation of your lung function tests. And on this paper, there were radiologists that actually scored the extent of fibrosis on the CT scan. They also measured the diameter of the mean pulmonary artery to the ascending outer ratio, which is there are two big vessels quite close one to each other that we know that they have been linked with the presence of pulmonary hypertension.

So, in essence, what this staging system showed is that if you have quite bad lung function with a CPI above 40, you are within a high risk group that the six year survival was measured 50%. So, this is quite ugly looking disease. If you have better lung function tests, but you actually, on the other hand, have evidence of fibrosis, or evidence of pulmonary hypertension, then you would fit that group. Otherwise you are at a low risk or have a good prognosis. This was tested in both a test and a validation cohort and similar results were found. So, in a way this has been validated.

The issue is that the outcome in the high risk group was bad despite treatment. So, what we need to do is that we are working at the moment in trying to identify those patients that are going to have treatment and these changes their natural history, changes the outcome of their disease. So, the data that would follow would try to question as to whether lung function tests could help with that.

So, we have largely defined patients with severe involvement if they have these kinds of characteristics, emphasizing that we may need to treat early to prevent any worsening. And in a study that we have performed, including patients since 2009, we saw that actually in the whole population, the six year survival is 87%. And actually, in the total Brompton group of patients, which is actually severe and advanced disease group patients, their lung function profile is quite preserved.

However, what we saw was when the gas transfer, which is one of the most important measurements in sarcoidosis, is below 40% of predicted then means a bad outcome and we have to be very concerned about the management of these patients. On top of that, we are looking at the figure that says anything between 40 and 60 is also starting to become concerning. So, we need to focus on our treatment in this particular group. When we grouped patients, depending on the lung function tests between mild and severe, we saw that there was a quite clear difference. And you can see here that the mild ones had very good prognosis with survival of more than 90% over time.

So, that’s what we currently are using to define our severity based on lung function tests. And we move on to the imaging, as I mentioned. And you can see here that the chest x-ray, this is defined since 1970, 1967, to be exact. But importantly, the presence of fibrosis as shown from our group cannot really be agreed among experienced radiologists. So, it’s not something that we can use to define change. And you can see very interesting cases where we have nodularity along the vessels, but also starting to see some areas that may be fibrotic underneath. But the changes among the sarcoidosis patients are so heterogeneous that we cannot really reach a very confident assessment of the extent of the fibrosis particularly because the distribution is predominantly in the middle upper lobes, as we can see here. And very often it is complicated by infections such as this one like an Aspergillus infection. Nonetheless, we are currently working on identifying whether there are specific patterns that would help us identify patients at high risk.

I would like to ask you, finishing off, that it is very important for you to get involved. And I think that together, we need to make a difference in providing a better care. And I would like to thank SarcoidosisUK once again for this wonderful event. Felix, back to you.

Dr. Chua: Vasilis, thank you very much for that excellent, excellent talk. You covered a very difficult area very nicely. I think we have Laura with us. I think Dr. Price has finished her other talk. And I think —

Dr. Laura Price: I am here. I’m just trying to work out the screen sharing.

Dr. Chua: Thank you, Laura. So, Laura, I’ve introduced you to the audience earlier. So, whenever you’re ready, just start, please.

Dr. Price: Amazing. Can you see my first slide?

Dr. Chua: Yes.

Dr. Price: Can you see me? Start video. Okay. Great. Okay. Well, it’s really fantastic to be here. Thank you so much for the invitation. As you, I’m sure, mentioned, I’m one of the respiratory consultants and I’m a full-time pulmonary hypertension clinician here at Royal Brompton working extremely closely with Vasilis all the team in the interstitial service. So, I’ve got a background in really managing patients with all kinds of pulmonary hypertension with the team here. And we’re one of the specialist pulmonary hypertension services. So, I thought in 20 minutes with a both patient and relative heavy audience, I tried to keep it fairly straightforward. I hope it’s clear to sort of understand why we need to get involved and why we need to detect this condition and this complication of sarcoid early. I’ll run through what it is, why it’s important, how we investigate patients and what we can try to do about it.

So, what is pulmonary hypertension? It’s a hemodynamic definition. It really is. It’s completely dependent on invasive characterization. And we know even though echoes are brilliant, we have incredible echo, staff and technicians here, we still need to confirm this diagnosis by a right heart catheter study. I put the numbers there for anyone interested. But essentially, this is a group of conditions with lots of different causes. And the problem is these vessels which are normally very, relatively thin walls and compliant and stretchy, here they are, become extremely thick walled and stiff, and even can occlude the lumen. So, this is the pulmonary circulation. It should be completely unlimited. As you exercise, you should be able to recruit and dilate the vessels in your lung blood supply to not limit you with exercise.

And as this develops in all kinds of pulmonary hypertension, I’ll call it PH. That’s the thing that happens. You’ll find when you’re sitting is when you start to walk. And you cannot recruit the vessels because they’re stiffened up. And this resistance to flow is what is the problem. And that is the backpressure that causes this problem with the right side of the heart. So, the RV should be thin, and crescent-like. This is a section through the heart. Here’s your big chunky left heart, the LV. And as this disease comes on, this is the right heart that gets swollen and overloaded. Ultimately, the walls get thick, that’s called hypertrophy. And in later cases, this right heart cannot cope. And you get right heart dysfunction, right heart failure and clinically you may develop ankle swelling, liver swelling, and what we call edema.

So, how common is this condition? I’ve called it a SAPH, so sarcoid associated pulmonary hypertension PH. We have registries where patients around the world with different populations of people suggest that this is a two, 3%, 20% prevalence is variable. And of course, it depends on the underlying stage of the sarcoid. It’s usually seen in patients with fibrosis, but not always. You can get no fibrosis and pulmonary hypertension in sarcoid rarely. And of course, we know that patients who are at the end of the sarcoid journey and may be assessed for lung transplant, this complication is really common. But what’s interesting is there’s quite a long latency period before it comes on. So, even after 15-20 years, this might still happen, and often in patients whose so acute inflammation in their sarcoid is what we call burnt out. And it’s quite often up to 17 years after the sarcoid diagnosis.

What causes it? This is what actually makes it very interesting to think about. It’s not one process, it’s usually due to this fibrosis and low oxygen in the lung. And that’s common to all patients with lung fibrosis. We know chronically low oxygen in the lungs, so alveolar hypoxia causes a level of thickening up of the lung blood vessels, and that’s common to everybody with lung scarring, lung fibrosis. But in sarcoid, it’s not just that. This is what we see in patients with PH in other cases, where there’s very big thickening up of the lung blood vessels, the pulmonary blood vessels. There’s sometimes liver involvement. Blood clots, really important, what we call group two pulmonary hypertension due to the left side of the heart, and rarely obliteration of the smaller pulmonary veins, and squishing of the large pulmonary veins, which can happen due to the sarcoid nodes. So, there’s lots of things to think about if this condition comes on.

We know from all kinds of lung fibrosis, that there’s no clear relationship between the level of lung fibrosis measured by the FBC on lung function, or a formal scoring system on the CT with the development of the mean mPAP pressure we measure, there’s no clear line relating those two. So, that’s suggesting there’s other causes. And indeed there are.

Remember that all patients with any lung disease, an exacerbation or an infection can really acutely raise pulmonary blood pressure. So, if you have an infection, or an exacerbation of a lung fibrosis, you will very usually have a degree of pulmonary hypertension that gets better quite quickly when your levels of oxygen get better. And there’s other reasons for it with intrinsic PIP, and things that happen in the lung that cause acute pulmonary hypertension. So, we would never formally assess somebody less than six to eight weeks after acute infection, because it’s going to be a falsely high level of pulmonary hypertension.

So, we classify common hypertension in our practice into five clinical groups. And that’s because the ones in group one are the most worrying. Sarcoid fits into group five. I’ll just let you know about the other groups, because when we think about somebody who’s developing pulmonary hypertension, we have to make sure we get this diagnosis and this subtype distinction, right, because it depends on this, it’s how we treat patients. So, sarcoid is in group five, because there’s multiple mechanisms as I intimated. But also, I think sarcoid can also have classification in all of our other groups. We can see the small pulmonary veins, we can see left heart problems. So, that’s group two pulmonary hypertension. Of course, group three with the pulmonary fibrosis component. But also, and very importantly, patients for sarcoid get more prevalent blood clots, six to eight times apparently, and they can be quite significant. So, we must always make sure we rule that out, either acute or chronic blood clots.

So, when might you suspect someone’s developing pulmonary hypertension. There’s a set of symptoms and signs which I’ve listed there, which may be quite subtle. When the right heart is developing dysfunction, there’s a symptom complex with edema. Also, when you walk, a dizziness which we call syncope, or presyncope, which is a very important symptom, and we worry about that. But usually, it’s very difficult to detect the subtle onset of an increase in breathlessness. These are the sorts of things as doctors and nurses, we would be looking for when things are more, you’re more breathless than we’d expect to the degree of a relatively stable lung picture otherwise, when there’s more dropping oxygen levels, when there’s more of a gas transfer, decrease. So, the very important findings of gas transfer, always important to think about the onset of pulmonary vascular disease.

BMP is a blood test, which it’s revolutionized what we do. And it’s very reassuring when it’s normal. If it’s up, it may be that the top chambers of the heart are stretched, it’s released on stretch from the heart chambers, and it can be very sensitive. Of course, echo, and CT, you look for particular signs, I’ll show you some of those. So, for example — how am I doing for time, halfway through. This is a patient without lung fibrosis. But you can see these are big pulmonary arteries that are bigger than they should be. This is the right heart border here. So, sometimes we see that’s a little bit big, the right heart itself, the ventricles in the front. So, it’s usually hard to see unless it’s very big, but we can see things even on a plain x-ray.

This is the CT, very important sign, where we look on, this is a plain CT without contrast. And you can see the central pulmonary artery is bigger than the adjacent aorta, and that’s the PA AO ratio that was discussed earlier. Now, we would always want, if possible, a scan that’s got contrast, because you can see when it’s well timed, how clear it is that that pulmonary artery trunk is bigger than the adjacent aorta. But we also look for lots of other things with the contrast scan, including the presence of blood clots, acute or chronic. We look at the ratio of the left, and that’s the right ventricle at the front, the left ventricle at the back, we can see how thick-wall the ventricle is, we can see how flattened the septum is, and many other things. So, we really appreciate having a contrast scan. When we’re looking at patients developing sarcoid PH.

No need to look too much in detail at this slide unless you wanted to. But this is the key test where we really need to understand the measurement of pulmonary hypertension. There’s some good YouTube videos of this on our patient websites, which is PHA-UK for all patients with PH and we’ve put this very slim plastic tube in to the venous system, usually through the arm veins or the leg veins, usually the arm in a day case procedure, and we move it through the heart. So, you have a right atrial pressure, a right ventricular pressure, a PA, pulmonary procedure artery pressure and ultimately a wedge pressure. But essentially to say that this inflammation gives us the absolute severity of diagnosis. And it’s extremely important to understand where the pressure is coming from. The wedge, for those interested, tells us that the blood pressure is coming from the left side of the heart.

The impact of pulmonary hypertension, and I’m sure it’s been discussed, it’s an adverse prognostic finding. And we know depending on the pressures [inaudible 00:33:27], it can be depending on that is where our curves of survival will go. So, this was a fairly old registry from France where all patients had what we call severe pulmonary hypertension. And it’s a curve akin to that with very low gas transfer and much less survival than if you don’t have pulmonary hypertension. But these are evolving areas. Ultimately, these are dependent on the severity of fibrosis itself. But again, in a population of patients with pulmonary hypertension, gas transfer above and below 35%, splits the curve, significantly splits the curve. The most discriminating factor, though, I think that’s really important is the amount of walking that’s possible. And in a six minute walk, walking less than 300 meters was very much less available than if, if you want more than 300 meters and of course, that’s got many factors associated with it.

Just a moment on how things work in the UK. We are one of the pulmonary hypertension nationally commission centers and there’s three in London. This is the team here and I’m hoping some of you on this call will recognize some of our team, as we work very cohesively, and I hope communicate well with you. Just to show you what we see as pulmonary hypertension teams and of all the patients, we look after most of our patients, almost half have got, group one, pulmonary arterial hypertension. So, of the sarcoid patients, for the amount of pulmonary hypertension work we do, actually, it’s a really small amount. It’s under 3%. And of course, that’s slightly higher in this hospital, but just to give you a flavor of what we do.

And what investigations might you need, if we’re thinking you might have pulmonary hypertension, these are the sorts of tests you would need to have. And just to explain why. We always look at these standard pulmonary hypertension markers. It’s about how much breathlessness you have. Quality of life is really important. And we thank you, I thank you all for filling out these forms. I’ll talk about that in a minute. Because we know in other kinds of pulmonary hypertension, quality of life improvement is associated with good outcomes. And we’re looking at that in patients with sarcoid PH. So, these are the tests that you might need to have. So, I think — Felix, I’ve got three minutes to go, am I allowed a couple more minutes or how do we do…?

Dr. Chua: Yes, of course. Take another minute or two.

Dr. Price: Yeah, fine. Okay, so these are the sorts of tests, I’ve kind of intimated them already. This is quite, this is our quality of life score. And I think it is, it’s all absolutely downloadable. But we really look at this with patients before and after treatment. And I think if it’s anything like other causes of PH, this is an endpoint is extremely valuable. We risk assess pulmonary hypertension, as in all kinds of PH. And we try to keep patients in these green columns, and it’s a multiple modal assessment modality, where we look at the symptoms, the presence of syncope, how much walking can be done, exercise assessment, and then hemodynamic assessment. And if patients have these red or yellow, we treat them more aggressively, and try to get the factors in the green because we know akin to other kinds of PH patients do better and survive better.

So, really briefly management is based on the drugs that we have, are based on endothelial function. And we have endothelin targets, nitric oxide pathway targets such as [inaudible 00:37:28] and tantalizingly on the horizon prostacyclin pathway targets.

This is from a review we wrote. It’s a bit complicated for today’s talk, but just to show you how we have to think about all the different associated factors that might drive pulmonary hypertension, and ultimately treatment of the sarcoid fibrosis is key, that we have to really think about the way we manage patients. Therapies, we use tablets, often in combination. These have not been studied in massive studies, but we know they’re safe. They don’t worsen [inaudible 00:38:06], which is a concern with lung function. And we know this, there’s a lot of new drugs coming out. So, this is a great area to be listening out for. There’s roles for lots of thinking together with our sarcoid team colleagues about whether immunosuppression needs to be increased. Sometimes the big vessels are stented. And of course, I’ve mentioned thinking about blood clots. That’s my summary. This is something that we really have to think about early. We know in other causes of PH treating early leads to better outcomes. And it’s really thinking about why it’s happening and what we can do. Thank you very much.

Dr. Chua: Laura, thank you very much for covering that very extensive and very complicated area, but a very important clinical part of what we do and what you help us with. Thank you so much. We’ve got questions. I will start with one for Dr. Kouranos. So, I think this is for Dr. Kouranos it says –it’s quite general. How do comments including ones from Dr. Kouranos, about respiratory breathing tests correlate to Dr. Anjali Crawshaw’s point, which was raised much earlier in the sense, how can they be normal when I think that my sarcoid is active? Vasilis, I think it’s a general question for you.

Dr. Kouranos: Yep. Laura, would you mind just answering? It’s not a problem, but just for that, for the benefit of the discussion. I would say that overall. This is something that we see very often in sarcoidosis. We do focus on the patient’s symptoms and try to see how the lung function test correlates with those. So, the inflammatory activity is something different from the disease severity. So, what we’re trying to assess is whether the patient has major organ involvement. We try to see what is the risk with regards to the patient’s life expectancy when performing lung function tests. If the patients have normal lung function, then that is a very key issue for both us and the patients; that their life expectancy is not going to be altered in the long run, or this is what we believe. Then with regards to the activity, we are, in a way, skipping the danger from the disease, and we’re going down to the quality of life. And we want to assess how much the activity that is reported by the patient influences their quality of life. And that is another key part of the decision making regarding treatment.

Dr. Chua: Thank you. Thank you, Vasilis. I think absolutely, I agree with that. The long and short is that lung function testing isn’t a test of a disease activity. It’s a test of how much the condition affects the lungs. And that output tells us how much we may expect the lung to be able to function in terms of what it’s designed to do, to conduct air around, to transfer oxygen, etc. Thank you very much. I think that’s correct. Because I think somebody else has a very similar question. I think I wanted to say that there aren’t any particularly excellent tests to define sarcoid activity. We have PET scans, of course, that look for activity in lymph nodes in particular organs, but not necessarily for the lungs, etc. But the tests that we do on a day to day basis to monitor patients, to decide how much treatment we give them or how much do we draw are based not so much on activity, but on severity and lung function is a good example of that. The next question is for Dr. Laura Price. Laura, is there a role for prophylactic vasodilator therapy for patients of pulmonary sarcoidosis?

Dr. Price: Sorry, I’m just going to stop sharing. So, that’s a really important question. No, not really. I mean, not. Because we know when you treat patients with pulmonary vasodilators who haven’t got pulmonary hypertension, you caused them to have an overspill, basically dilating effect on their systemic blood vessels. And they can develop over time, a high cardiac output failure syndrome. So, it’s really not a good idea. And we know that we are very cautious and rightly so with our treatments because they have side effects. But when pulmonary hypertension does happen, these are usually very well tolerated drugs when pulmonary hypertension happens. So, in summary, we wouldn’t prevent PH by using pulmonary hypertension drugs until the onset of PH.

But there’s other things you could think about, I think it’s important to be aware of it. If there’s a change in your symptoms, or an onset of breathlessness, or disproportionate change in the gas transfer, if you’re dropping oxygen, more than you should, those are the things you should speak to your sarcoid doctor about. And it’s not common, but it’s common enough to always — we always think of it, don’t we? So, I think it’s in terms of preventing it. There’s also some logic in terms of getting on top of infections, treating infections promptly. We know in other causes of lung disease, repeated exacerbations probably do drive in inflammatory vasculopathy. So, these are the sorts of hypothetical things; not to think about it all the time, but just to be aware that there’s probably some sensible things you could do.

Dr. Chua: Great. Laura, thank you very much. The next question is for you too, there’s a follow up question. Is lymphedema classified as a sign of PH? I have secondary lymphedema as a result of sarcoidosis in the lungs and the lymphatic system, but is lymphedema associated with or recognized as part of the spectrum of PH?

Dr. Price: It’s a great question. I mean, it’s — I’m sorry you’ve got lymphedema, it’s not at all the same as PH. So, we have a few patients with both. PH swelling relates to the right heart, that’s the primary problem. So, your lymphatic drainage into the right heart is limited because the right heart is not working properly. It’s not the same. So, lymphedema is a lymphatic peripheral problem, not due to a right heart problem.

Dr. Chua: Great. Laura, thank you very much for that succinct answer. I think those are all the questions we’ve got for this session. If there are other ones are trying to insert a reply to them. John, I think Mr. John Devine is waiting to ask a question. We’ll take one question, John, because I think we need to go. We’ve got four minutes before Dr. Peter George starts the next session. So, let’s take a question from John.

John: So, these are questions that were sent in in advance actually from the UK sarcoidosis patient questions. I don’t know how many we’ll do. I’ll work through as quickly as possible. So, just want to quickly say my partner who watched my video for the first time said that I was a bit too blasé and optimistic. And she said she wanted to let you know, it’s been hard living with sarcoidosis these years, and there actually have been some really difficult times. And the last two years have been especially tricky. And it’s been the anxiety of the disease. So, he thought I was a little bit too bobby, it’s been hard. Anyway, first question is coming from people from outside is just a suggestion is what is the latest view on the effects of COVID on patients with pulmonary sarcoidosis, especially many of whom will be on steroids and methotrexate. And one person in particular said that they’ve got very limited lung function, they had COVID. They seem to have got rid of the COVID, but they’re still left with strong breathing issues. So, is there any latest information on the issue that’s obviously been worrying and affecting a lot of people over the last few years?

Dr. Chua: Can I take the question? I’ll take your question quickly. And I’m going to answer it by separating it into two branches of answers, John. Firstly, I think, a lot of people have been asking, is if they’ve got sarcoid of different severity, they get COVID; are they able to access the antivirals and other treatment that’s now been online available since December? I’ll come back to that. The first question I think is the first part is I’ve got sarcoidosis of mild, moderate or severe disease. What will happen? What can I expect to happen to me if I pick up COVID? Firstly, nothing very much may happen to you. You may develop mild symptoms of upper respiratory tract, cold, for example, particularly if you’re fully vaccinated and boosted. So, if you’ve had a primary vaccine course of two vaccines, and then one booster or two boosters, you’re likely to just get mild disease. And that’s true for sarcoid. We did actually have these questions at the first meeting last year, and they’re very, very important questions.

But the experience to date mirrors what we knew a year ago, that patients with sarcoidosis largely do not get severe complications from COVID-19. That’s not coming through in reports being published, et cetera, et cetera. But of course, people with severe disease of any cause; IPF, sarcoidosis, connective tissue lung disease, are more at risk of getting complications from COVID. Now, although sarcoid is not on the treatment list, issued in December on December 16, in the UK to access antivirals and monoclonal antibodies, or what we call n MAbs, patients can access the treatment if they’re on more than 10 milligrams of prednisone a day or they’re on methotrexate and other immunosuppressants. So, it’s not that the disease doesn’t allow you to get those treatments, but you can access treatment if you’re deemed to be immune suppressed, according to that list.

So, GPs, etc., will have that list we certainly do, and how you access them if you pick up COVID-19 is you ring 111, and there’s a national database of notification for diagnosis, then you’ll be advised to go to your nearest center to get the treatment and those centers are called the CMDUs. So, that information is all online. I hope I’ve covered both branches of that question about severity and what you could expect from COVID and the novel treatments for patients. John, that’s a great question. Thank you for joining the session. I think we have to give up our space and time to the next session. But I hope — I look forward to seeing you in the clinic. And let’s move to Dr. Peter George for the next session.