Correct diagnosis of Idiopathic Pulmonary Fibrosis (IPF) (2016)
The two international experts Prof. Dr. Claus-Peter Heussel and Prof. Dr. Michael Kreuter (both from the Thoraxklinik, University of Heidelberg, Germany), discuss the diagnosis of a patient with idiopathic pulmonary fibrosis. They describe in detail the diagnostic journey and pay special attention to high-resolution CT scans (HRCTs) and the successful collaboration between radiologists and pulmonologists.
MK: Slide 2 - first of all it’s my pleasure to introduce my colleague to you – this is Claus Peter Heussel, he’s professor of radiology working at the University hospital of Heidelberg and he is the head of the department of radiology at the Thoraxklinik, which is a chest clinic here in Heidelberg. And Professor Heussel: Great that you are here and I’m looking very much forward to nice discussions with you.
CPH: Slide 3 - Thank you so much, Michael. This is Professor Michael Kreuter, he is the head of rare and interstitial lung diseases here at the Heidelberg University Thoraxklinik and we will jointly make this nice webinar together with you.
B- Case presentation- Part1 Diagnosis- Anamnesis
MK: Slide 4 - Well, let’s start with our case which we would like to discuss with you. The patient. We know that patient since a couple of years, presented first in 2009.
MK: Slide 5 - At that time, he was a 69 years old male patient and he was complaining on increasing dyspnoea on exertion for over 1,5 years. At that time, he was possible to climb three flights of stairs and also still some sport was possible, for instance the patient loved to cycle. He had no cardiac problems, meaning no angina and also he was not, at that time, complaining cough under exertion. Well, for the clinical work up of a patient with an interstitial lung disease we need a couple of investigations. And one of the first is for sure the clinical examination.
MK: Slide 6 - And in that patient, he was a normal weight patient of 87 kg and he was 185 cm tall. In the auscultation we could hear bibasilar pulmonary velcro crackles. He had a heart rate of 54 beats/min, however, no heart murmurs and no leg oedema. As a second very important thing in the diagnostic work up of interstitial lung disease is a very thorough work up of the medical history and of pre-existing conditions, which means we shall ask the patient about his history, why he presented, that’s what I just told you, the increasing dyspnoea on exertion, but also others like his family history,
MK: Slide 7 - which was in this patient uneventful, he was working as an office employee, he had no allergies, he had no exposures, he was an ex-smoker – stopped two years before the first presentation at our centre and he had 40 pack years in total of smoking. Another very important question on the question of differential diagnosis in interstitial lung disease is the question for drugs. However, in the patient there was no medication at first presentation which may have caused the interstitial lung disease, we are going to discuss a little bit further with the radiologist later. Also, pre-existing conditions meaning comorbidities are very essential in the work up of patients with interstitial lung disease. That patient had a pneumonia a year ago which might have been one of the first clinical signs of interstitial lung disease, however, this is always very hard to tell. Also, he had some minor urological surgery 15 years ago. And also, and we do not know up to the day what is the cause of that, that patient had a mild hepatopathy of unknown aetiology. Also, in the clinical work up of a patient with interstitial lung disease we have to perform pulmonary function tests.
MK: Slide 8 - Here you can see the results of that. You see that he has some slightly impaired vital capacity of 73 %. Also, we have to look at the diffusion capacity which was also only mildly impaired with 66 %. Blood gas analyses addressed were normal, the PaO2 of 72 mmHg. And also we always look at whether the patient has also an obstructive lung disease, looking here at the Tiffeneau index meaning the ratio of FEV1/FVC and you see that it’s normal in the patient. However, I think one of the important things is a regular pulmonary function test does not rule out interstitial lung disease. However, taken together, in that patient we see some slightly impaired diffusion capacity and again mild restrictive lung disease. What we also do in these patients is a six-minute walking distance. You see here 520 m and the initial saturation is 96 %, however under exertion it dropped down to 91 % which is corresponding to the slightly impaired diffusion capacity. Well again, looking at how to diagnose interstitial lung diseases especially in the work up under the suspicion of idiopathic pulmonary fibrosis or under other idiopathic interstitial pneumonias we have to rule out for instance connective tissue disease. This is something in the combination of clinical work up with history and also with autoantibodies.
MK: Slide 9 - In that patient we had an autoantibody screening which was uneventful for all those you can see here on the list. And also which should be included is a laboratory profile – you see here only mildly elevated transaminases which is corresponding to his mild hepatopathy of unknown aetiology. We also screen these patients for pulmonary hypertension which includes on the one hand the BNP which was normal in that patient. A little bit later we’ll show you the echo which is on one hand something we perform to rule out dyspnoea of other cause than the interstitial lung disease and also as a screening tool for pulmonary hypertension. What we in Europe do, mainly but I know that there are other centres which do not do is to perform bronchoalveolar lavage in patients under the suspicion of interstitial lung disease mainly for differential diagnosis work up especially to rule out hypersensitivity pneumonitis, especially if BAL shows a lymphocytosis of more than 40 % or sometimes more than 30 % which may be a hint for another underlying interstitial lung disease for instance hypersensitivity pneumonitis. However, in that patient it showed a regular cellular pattern.
MK: Slide 10 - Here, as I already told you, you can see the results of the echocardiography which showed a regular left ventricular function and normal diastolic function. We also focus very much on the right ventricular function and on the pulmonary artery systolic pressures which were normal in that patient but still again a normal BNP and a normal echo do not rule out pulmonary hypertension. And all the rest only showed a mild sclerosis of the mitral and of the aortic valves.
B Case presentation- Part 1 Diagnosis- HRCT I
MK: Slide 11 - One of the most essential things in diagnosing interstitial lung disease is that you are working close together with a very well-known and a very elaborated radiologist and so it’s my pleasure now to hand over to Claus Peter Heussel to discuss with you the HRCT which we have undertaken.
CPH: Slide 11 - Thank you, Michael, for sending this patient to my department. And he was sent to my department with the question of a interstitial lung disease. So, according to the ATS guidelines we performed a thin section high resolution multi-slice CT in this patient and since it’s interstitial lung disease we don’t need any contrast agent to investigate that, that means it’s easier to organise, no real impairment has to be ruled out beforehand and these are the images that we acquired here.
CPH: Slide 11 - So, what you see is obviously this CT is not normal. And now we have to analyse the patterns in detail a little bit more and I’ve drawn some markers here and you see there is a ground-glass opacification. So, the definition of ground-glass opacification is that you have an increased lung density as compared to the remaining lung tissue while the underlying lung architecture that means the vessels and the arteries and veins are still visible. And this is the case in this patient. We have several regions of ground-glass opacification, not only in these regions of interest but also at different places in a smaller proportion and I have drawn therefore a huge region of interest in the left lower lobe which almost covers this complete left lower lobe. There is a patchy pattern of ground-glass opacification in the left lower lobe.
CPH: Slide 12 - Furthermore, we detected in these regions, a little bit more upwards in this patient, a severe peripheral dominant reticular pattern. That means you have streaky linear findings mainly along the subpleural spaces, sometimes they are confluent to each other and the single reticulation is not anymore distinguishable. Of course, there is also some ground-glass opacification in these regions of interest. The third place I’ve shown you here in the left lower lobe there is also a relevant amount of ground glass but the majority in these regions is reticulation pattern.
CPH: Slide 13 - Finally, there is a, in the more apical the reticulation is evident and in the most subpleural spaces you see those black holes which are air-filled air space cysts and that is the honeycombing here at this time point of the disease, we have only a single layer of honeycombing in the neighbourhood of severe reticulation. And also in the more basal parts you see in segment 6 on the right hand side and on the left hand side some beginning honeycombings. So, this is, according to the ATS guidelines, a distribution of a pattern of severe interstitial lung disease which is probable or typical for UIP.
CPH: Slide 14 - And at the very end I will show you the traction bronchiectasis which also belongs to this pattern of UIP. You see the dilated bronchi going along in the bronchovascular bundle with the pulmonary artery, they have the same or even a larger diameter as compared to the bronchopulmonary artery, therefore it’s a traction bronchiectasis on the right hand side. And here in the subsegmental places you see several of those small but very evident traction bronchiectasis.
CPH: Slide 15 - I already mentioned a little bit the distribution of the disease, therefore I brought such a sagittal reformat with me which corresponds more or less to a lateral view. And using this makes it very easy to have an overview of the distribution, whether the disease is more apical or more basal dominant and you see the more apical parts of the lung are not or almost not affected while the more basal parts of the disease are very much affected and that is also something that is very typical for typical UIP pattern.
MK: Slide 15 - Great, may I just comment?
CPH: Slide 15 - Yeah, give your opinion!
MK: Slide 15 - Now, and this is something for our colleagues, now you know why that is so essential to have a good radiologist because it’s possible that you learn a lot in the discussion with him and I think we have on a more than daily basis many discussions on different patterns and this is sometimes not easy to pick the right answer on that and also that’s why I like it very much to have a multidisciplinary discussion in the truest meaning of the word because then we really can discuss what we see.
CPH: Slide 15 - So yeah, and that’s why we always have these kind of daily discussions also in the routine and why I’m … it’s my task to present you the image in a quality that you can follow my report. And that I do not only give you a written report but I show you what I’m reporting on so that you see whether I’m right or whether I’m even wrong.
CPH: Slide 15 - So, let’s come to a question to you which is a difficult combination question: So, which is the correct answer? Is it pattern A – is it a traction bronchiectasis as well as pattern B? Or is the correct answer: A and B are both honeycombing? Or is it more difficult and A is honeycombing and B is traction bronchiectasis? Or is it just the other way round – A is traction bronchiectasis and B is honeycombing? So, please give your vote now. And let’s check the answers of the auditorium. So the vast majority of listeners has rated correctly, number 3 is correct.
CPH: Slide 16 - So, let’s come to a question to you which is a difficult combination question: So, which is the correct answer? Is it pattern A – is it a traction bronchiectasis as well as pattern B? Or is the correct answer: A and B are both honeycombing? Or is it more difficult and A is honeycombing and B is traction bronchiectasis? Or is it just the other way round – A is traction bronchiectasis and B is honeycombing? So, please give your vote now. And let’s check the answers of the auditorium. So the vast majority of listeners has rated correctly, number 3 is correct.
CPH: Slide 17 - So, pattern A is honeycombing and it contains air which is as black as the surrounding Heidelberg air while pattern B is a traction bronchiectasis, so it’s a widened bronchus going along with the bronchopulmonary vessel giving us a traction bronchiectasis.
CPH: Slide 18 - So, as a summary from, of the CT which has been taken in 2009 we see that the pattern that we altogether found is very consistent with a typical UIP pattern even though the extent of honeycombing is minimal but there are several places of single layers of clear honeycombing. So, I would state here this is typical UIP pattern. On the other hand, we have to take care about the ground-glass opacification – whether ground-glass opacification is a part of UIP, however it should not be the majority of the disease. So, if there is more ground glass than reticulation then it would, it is not compatible with UIP - in this case we have so much reticulation that the ground-glass opacity is even less. This ground glass may indicate an acute inflammation or the acute inflammatory part of the disease and here it’s in the background, so I’m still consistent with a typical UIP pattern.
CPH: Slide 19 - Therefore, I would give you this answer in my report, Michael: this patient is a patient with typical UIP pattern which is a pattern only, it’s not a disease and now it’s our joint task to find out which is the underlying disease and this might include IPF, collagenosis, asbestosis, drug-induced interstitial lung disease, HP, familial interstitial pneumonias or even rare aetiologies which I even don’t know about. So, therefore I would like to hand over this case in my specialty team and demonstrate you this typical UIP pattern for further diagnosis
MK: Slide 19 - And I think that’s why it’s so essential to have a multidisciplinary team discussion because all these differential diagnoses is nothing I alone as the clinician or Claus Peter Heussel as the radiologist or our pathologist can solve. Only in the assumption and only if you look all of the different points together we can then answer what the underlying disease is. And if we then look together at that patient, so we don’t see another cause causing the interstitial lung disease, no drugs, no connective tissue disease, no exposures for instance no asbestos, no familial interstitial lung disease and so on. And that’s the reason why we then in our multidisciplinary team, which consists of a radiologist, of a pathologist and of a couple of clinicians, why we then came to the diagnosis of IPF.
CPH: Slide 19 - why don’t you give those questions to the patient beforehand, before you send them to CT scan?
MK: Slide 19 - That’s a very good question. So, the work up of interstitial lung disease is a very elaborated one. So, at least in our centre, what we do is we see our patients which are being referred from other colleagues - GPs or many other pulmonologists for the work up. And most of these patients, these patients already have a CT – that’s one, but the other very important thing is you have seen that I’ve written that the patient has bibasilar velcro crackles, inspiratory crackles, which is something which shows very, very, very much in the direction of a fibrosing interstitial lung disease and you need a very good CT during all the work up, however, at the final end then it is important to rule out other causes of what you see in the CT of the fibrotic interstitial lung disease.
MK: Slide 20 - However, now we would like to give you the next question.
CPH: Slide 20 - So, the next question is: Does this need for the correct diagnosis of IPF…. Which is not true, which of the answers? Does it need a multidisciplinary team discussion focussing on the clinical, radiological and if necessary the pathological criteria? Or does a correct diagnosis of IPF need a contrast enhanced CT scan? Or 3: Does it need the exclusion of secondary causes such as drug-induced interstitial lung disease, chronic HP or connective tissue disease? So, please give us your vote!
MK: Slide 20 - Claus Peter, would you like to comment on the answers?
CPH: Slide 21 - Yeah, the vast majority of the auditorium has correctly answered number 2. So, it is not necessary to apply contrast agent and that is a key because if you send such a patient to my department with only the diagnosis or the suspicion of dyspnoea, let’s say, then I have to apply contrast agent, for instance to rule out pulmonary embolism or to look for enlarged lymph nodes or even a bronchocarcinoma for staging. So, it is very valuable if you give me the information about interstitial lung disease, so I can avoid contrast application. Furthermore, if I apply contrast agent then it’s a lot to the kidneys, maybe, and it mimics a ground-glass opacification and then I have a CT scan that shows a lot of ground glass while this might be caused by the application of contrast agent which is false positively giving a acute inflammatory disease. All the other answers have been answered beforehand. So, by the discussion with an interdisciplinary team every partner is able to demonstrate the confidentiality of his treatment, of his pattern, whether there was a mix-up or whatever. So, that is very helpful to discuss this together and jointly.
MK: Slide 21 - So, maybe just to underline what Claus Peter just said, just think if you send a patient to a radiologist what is not only the answer you’re awaiting from him but also please consider what question you pose to him. Because if you just say to him: that patient’s having dyspnoea, he needs a contrast enhanced CT, right, because to rule out for instance pulmonary embolism. So, if you have a suspicion on interstitial lung disease, it would be very good and helpful to you and your radiologist to tell your clinical partner, the radiologist, to tell him what your suspicion is because only then he can describe you and he can utilise the correct mode of CT. Well, if you then have, after the thorough discussion in the multidisciplinary team, if you then have the diagnosis, then, only then you can discuss on the therapeutic options and again, before you start to discuss on what kind of therapy may be applied you have to have a correct diagnosis.
B Case presentation- Part 3- Longitudinal HRCT
MK: Slide 30 - And maybe, Claus Peter do you like to comment on the multi-slice CTs now we have a couple of years after we made the first diagnosis?
CPH: Slide 31 - Yes, thank you Michael for this opportunity to give you an overview of seven years of multi-slice CT scanning in this patient. Just recently the patient was again in our department and therefore I can now give you an overview how these particular patterns developed in detail over time. So let’s see how lung changed in this region. This slide you already know, this was taken in 2009. And you remember there was a ground glass opacification at these places. And there was also reticulation in these areas. And this developed in 2014 in more reticulation. So the ground glass didn´t disappear completely but it changed into reticulation. And there, now we have much less ground glass. On the other hand, the reticulation, especially in the dependent part of the right lower lobe, this developed into honeycombing. Now we have air-filled air space cysts now in several layers along the subpleural space. So, this is now typical honeycombing also on the left hand side. And, even in the recent CT scan, we see there is now the reticulation is even progressing. There is still a little bit of ground glass opacification indicating the acute inflammation of this patient. And it developed even more into reticulation. However, the place with the honeycombing – there was still a little growth of honeycombing, but not such severe as other parts.
CPH: Slide 32 - Another place of the disease is shown here. You already know this slide. There was very mild honeycombing, there was a traction bronchiectasis, you see this ectatic bronchus along the bronchovascular bundle, you see the reticulation in the subpleural space confluenting and the traction bronchiectasis got a little bit more during the course to 2014. While the reticulation developed into honeycombing it´s now air-space filled cysts as black as
CPH: Slide 32 - the surrounding air. And also this reticulation grew significantly and also here some honeycombing developed. And, in the further course you see the traction bronchiectasis was in a similar way maybe a little bit more enlarged during over time. And also here the honeycombing increased and the reticulation was a little bit increasing over time. So, this is the typical course of such a disease. The end stage where the inflammated regions with ground glass developed into reticulation and they developed into more traction bronchiectasis and honeycombing. This is the end stage of the disease. There is no way back for these regions. So the idea is to decrease the speed of the development of those patterns. Michael, are these wordings, is that adequate that we use this wording or do we sometimes hide the findings in our reports and we are maybe not be able to identify the patterns in the reports?
MK: Slide 32 - So, maybe I would like to answer a little bit differently. Why is it so essential that we know all these different patterns and why is it so essential that we, as the pulmonologists, as the clinicians, that we can really read what kind of different patterns we really see? I think especially the identification of ground glass opacification is in a patient with a fibrosing interstitial lung disease and especially in IPF very, very important. Why? Because we as the clinicians see a patient who comes into our centre as an in- or an outpatient and he´s presenting with a new symptom. And that that new symptom means dyspnoea or a curating cough we have to decide on whether that patient could have on a clinical diagnosis acute exacerbation. An acute exacerbation means an HRCT would have to be done at the same time very fast. And I think you, we, as clinicians we shall read what we can see there and I think therefore it is so essential that we can differentiate between all these different patterns. And if you list all these four you have just here on your slide I think we as clinicians have to really read what the different patterns are. And I think again, if we don´t know it we have to discuss with our radiologist and learn together from each other.
CPH: Slide 33 - So, let´s use this opportunity to check whether you know all the patterns that we have heard about today. So, what are these areas named? What can we see in here? Is this grey marked area, is it honeycombing? Is it reticulation? Is it traction bronchiectasis? Or four, is it ground glass opacification? As I mention before, sometimes there is a combination of diseases and here you have now to decide because I have stated clearly only one pattern. You have to decide what is the majority of the disease. Is it more, is it more honeycombing, more reticulation, more traction bronchiectasis or ground glass opacification? So we come to the answers. So, the majority, about 2/3 of you have chosen honeycombing as the right answer. Which is obviously not the idea that I had in this slide.
CPH: Slide 34 - Honeycombing is not wrong, let’s say, however it belongs altogether to the reticulation there is probably or there is for sure some honeycombing in these areas marked, but the majority of disease, of pattern in these areas is the reticulation.
MK: Slide 34 - Well you just asked me why is it so essential for us as clinicians to identify all this different patterns. Why is it for you as a radiologist so important to know all these differential diagnoses for all these different patterns or let’s say to differentiate between NSIP pattern, between UIP pattern, organizing pneumonia pattern, LIP pattern and so on?
CPH: Slide 34 - Ja, it’s the one part of the answer is of cause the clinical issue and the prognosis of the patient is very different and I as a radiologist I am frequently not aware of that. I think a lung fibrosis is only a side diagnosis and there is no need to characterize that in detail. However, if I am doing a let’s say, an abdominal ct scan and in an abdominal ct scan the most, mostly affected regions of the lung, the basal lung areas are also shown in the lung window level setting, its only one click away, I can see those regions and it’s my task to report there is a lung fibrosis and even more to characterize even if its a abdominal ct scan. On the other hand, also in cardiac ct which might be done since the patient suffers from dyspnea, I might see a severe lung fibrosis. And this might be the main diagnosis for the patient and his prognosis might be mainly influenced by this fibrosis more than by the possible findings in the cardiac ct. So, for me it’s, it’s essential to know what you suffer in this, what’s your differential diagnosis in this patient, what he suffers from and whether this might be a prognosis related disease that I am finding not necessarily as a side finding.
CPH: Slide 35 - So, let’s check the second pattern to analyse. So what is the marked area here, I think this is a little bit easier and more clear for you. Is it honeycombing, is it again a reticulation pattern, is it a traction bronchiectasis or is it ground glass opacification?
CPH: Slide 36 - So, ja, this answer obviously was a little bit easier, its more clearly it’s not in the subpleural space, therefore honeycombing and reticulation are less attractive for you and this is very clear it’s a very severely dilatated bronchus along a bronchovascular bundle, so therefore the right answer is traction bronchiectasis and more than 90 % of you have chosen that.
MK: Slide 36 - I think maybe another statement why the radiologist has a little bit to know about the differential diagnosis. If we have a patient for instance, we are discussing the NSIP pattern and then the radiologist knows about the differential diagnosis he only, does not only look on the lungs he also looks at different things for instance he describes me, because he knows that for instance a patient with a fibrotic interstitial lung disease may have some other combinations of diseases for instance a fibrosis of the liver, and then he says: “Oh, here Michael you see, I also see a fibrosis of the liver and I heard that there are diseases which are very rare like telomeropathies which is a prime, which is a prior aging of the patients. And then he describes “Look here, we have two things”, what about, did he grey very early and so on. And that may help us again to look not only at the interstitial lung disease but again focussing on the aetiology.
CPH: Slide 36 - So other side, finding might be also dilatated esophagus or gynecomastia or effusion or pericardial fusion, so things that we might not always report or be aware of because it might be almost normal and only a side effect or side peril and so you ask us really to describe all these findings and to discuss that also in the MDT, okay? Thank you!
CPH: Slide 37 - So, we come to the next question. Again, not so difficult: Is it honeycombing, is it reticulation that is more in this yellow roi or is it traction bronchiectasis or is it ground glass opacification. Always very clear what is the main finding here.
CPH: Slide 38 - And very clear answer, the vast majority of you has, have answered that this yellow marked region suffers to ground glass opacification, that’s right. Here we have an increased lung density while the underling lung architecture, those vessels which we can depict in this area, they are still visible or ever the lung density itself is a little bit increased, so this is an interstitial infiltration and the name for that is ground glass opacification.
B Case presentation- Part 4- Take home messages and conclusion
MK: Slide 39 - Well, then we would like to finish with this case, and I think we made it very clearly: The discussion in a multidisciplinary team is essential for the diagnosis of interstitial lung diseases including but not only for the correct diagnosis of idiopathic pulmonary fibrosis. And it’s not only that he hands me over his support and I hand him over my question, it’s a real discussion like we are doing today. And that is on the one hand something where you can learn from each other and the other thing is that’s where you only can state where the diagnosis is. Well, thank you very much for discussion with me Klaus Peter [Thank you] and that you all listened
MK: Slide 39 - Bye bye.
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Raghu G., et al. An official ATS/ERS/JRS/ALAT statement: idiopathic pulmonary fibrosis: evidence-based guidelines for diagnosis and management. Am J Respir Crit Care Med 2011;183:788–824.
Raghu G., et al. An Official ATS/ERS/JRS/ALAT Clinical Practice Guideline: Treatment of Idiopathic Pulmonary Fibrosis. An Update of the 2011 Clinical Practice Guideline. Am J Respir Crit Care Med 2015;192:e3–e19.