Beyond Borders: Exploring Interstitial Pneumonia with Autoimmune Features (IPAF) 

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OK, So hi everyone.

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Thank you for coming today attending the Rheumatology ILD Master Class and titled

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Beyond Borders:exploring interstitial pneumonia with

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auto immune features with Doctor Janet Pope and Doctor Daniel Marinescu.

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My name is Caroline Vo,
and I'm a rheumatologist and it's my

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pleasure today to moderate this evening's program and introduce you to tonight's

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speakers.

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So today we have Doctor Janet Pope, who is a rheumatologist.

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She's a Professor of Medicine in Rheumatology at the University of

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Western Ontario School of Medicine.

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She has published over 600 articles resulting in several research accolades

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and is also a passionate teacher educator, especially in rheumatoid arthritis,

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lupus and scleroderma.

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She currently Co-hosts some of the Around the Rheum podcasts after having been

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featured as a regular guest.

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Janet has a social media presence on Twitter
@janetbirdope where her

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#clinicalpearls have a reputation of teaching physical findings to more than

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20,000 followers.

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We alongside of Doctor Janet Pope,
we also have Doctor Daniel Marinescu who

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received his medical degree from McGill University and completed residency

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training in Internal Medicine and Respirology at the University of Toronto.

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He subsequently completed the two year fellowship in Interstitial Lung Disease

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and Master of Health Science at the University of British Columbia,

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Columbia with a focus in epidemiology and clinical research.

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He is a clinical Assistant Professor in
the Department of Medicine at UBC and A

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and a post Doctoral Research Fellow with the Center for Heart Lung Innovation.

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He works as a respirologist at Vancouver General Hospital at the Lung Center.

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Dr.

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Marinescu's research focuses on the morphology and diagnosis of ILD,

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with which he has studied at the Care-PF, the largest prospective registry of

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patient with fibrotic ILD in the world.

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He is interested in understanding how genetics contribute to ILD and its

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clinical outcomes which he hopes will be to

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improve diagnosis and personalized care in this challenging disease.

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So oh, sorry,
I forgot to change the slides.

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And so today before we start,
I have some few housekeeping items I have

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to mention.

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First,
we ask ask you to provide feedback at the

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conclusion of this event by completing the session evaluation that you will have

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the link at the end of the session in the chat box.

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We truly appreciate you taking the time to provide feedback as it helps

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to shape future programs and ensure that we are developing medical education

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programs that provides value. To ensure the best possible sound quality for

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everyone attending.

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Please note that all participants should be muted.

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If you have any question,
please write your question in the chat

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box and we will be able to ask those questions at the end of the presentation.

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Please note also that this presentation
is being recorded so people that won't be

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able to to attend this webinar could listen to it later on.

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And feel free to open your camera so it can be more interactive for the

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presentation and for the presentator as well.

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Before we start,
it is important to note that this program

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has received financial support that the faculty has received an honorary room for

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their participation.

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However,
the faculty is fully responsible

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for developing all content in this learning activity to achieve scientific

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integrity, objectivity and balance.

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So there there is no mitigated bias.

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Here are my faculty disclosure.

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I did have some some fees from BI as a presentator and also tonight as a

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moderator.

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And here are the faculty disclosures for Doctor Pope and for Doctor Marinescu.

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So without further ado,
here are the learning objective for

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tonight.

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We will be understanding the clinical manifestation of IPAF,

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discussing treatment options for IPAF and illustrating the importance of

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collaboration between astrologist and rheumatologists in managing

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patient with IPAF.

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So without further ado,
I will leave Doctor the presentators to

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start their presentation.

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Great.

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Thank you, Caroline.

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And we thought we would like to do something interesting,

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a case where maybe you know,
Rheum asked RASP and another case for
resps

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asked Rheum.

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So this one we're starting.

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And Daniel, am I starting or are you?

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Oh, feel free to feel free to start.

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Yeah.

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All right.

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Because we, we know these cases.

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We came up with them.

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So 67 year old man referred to rheumatology from the emergency room.

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So, 50 Pack/yr smoker quit two years ago because of the birth of his granddaughter,

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so it really motivated him with a little baby around.

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So he presented to the emergency room.

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He had an abnormal chest X-ray.

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You can see at the bases they are quite abnormal.

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He had some joint pain and why they did a rheumatoid factor in the emergency room

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is a little bit beyond me, but it was strongly positive.

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So the question they sent him to rheumatology is,

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is this rheumatoid arthritis?

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So obviously with the abnormal chest X-ray,

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somebody also quite appropriately ordered a
CT scan and you can see some changes

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there.

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And Daniel, can I ask just briefly, what, what would you say?

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I can tell it's abnormal as a rheumatologist, but what would you say?

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Yeah, sounds good.

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Happy to.

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So, so there's it's only one slice, but it,

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it seems like it would usually we're dealing with disease that's more basal

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predominant and it seems like this might be the case here as well,

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although it's hard to tell without kind of scrolling through all of it. 

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And we have mostly peripheral I would say both evidence of reticulation and

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fibrosis in the kind of the lines, extra lines that you see there,

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but also within it there's kind of an admixed ground glass.

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So both a bit of reticulation and a bit of ground glass,

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and there might even be some places where you can imagine - this isn't a great

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textbook example of subplural sparing.

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I, would never put it in a textbook, but you can with the eye of faith,

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maybe think about that.

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So a more difficult pattern,
but you would maybe air towards the side

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of something looking something towards NSIP if you had to put a label.

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So really quite helpful that we knew something obviously was going on in his

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lungs.

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So for many of you listening,
you know that rheumatoid arthritis is

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associated with ILD more a UIP pattern, but just about any pattern you could

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think of that's interstitial could be associated.

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So UIP, NSIP and some other patterns as well.

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It's relevant it,
it's more common than this,

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but it's about 7% of women and 8 to 10% of men will have relevant ILD.

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By that I mean progressive where we Co manage with our respirology colleagues

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and where it's going to cause big problems down the road.

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It is more common in positive RF possibly in men.

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There's always more women with it because 80% of RA is women.

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But the proportion of men having ILD is a bit higher, smokers, older age,

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longer disease duration, sometimes asthma, not usually.

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So there's some other associations and bad disease activity.

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So having gotten into damage like some of these hands here, you see a lot of damage,

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extra articular like nodules because of being
CR positive, more apt to get it.

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So bad disease activity equals higher chance of ILD over the years they have it.

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And to not forget,
there's a lot of lung manifestations of

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RA.

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So really from airway at the top with tracheal things and cartilage issues up

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to and included including you can get COP, you can get the interstitial lung disease,

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but you can have reactive airways and emphysema changes even in non-smokers

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with RA,
pleural disease and pulmonary

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hypertension to name some of many.

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So we have to think and we don't really put methotrexate lung on this list,

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just telling you they're right there because that's that happens,

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but very rare.

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The other weird thing is that this is 11, 000 patients from a Swedish registry.

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So these are population patients, patients with RA.

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They tried to verify the thing like the code that they really had RA.

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So this isn't a selected population and they compared to age, sex,

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match region controls and what they found was respiratory problems even five years

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before RA diagnosis were about 60% higher, so about a 1.6 odds ratio or hazard ratio.

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So even before you have your RA,
you might be getting lung problems that

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could be emphysema,
could be interstitial lung disease,

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could even be reactive airways.

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So we're expanding what we're understanding of RA as doing something

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bad to the lungs or conversely lungs precipitating RA,

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which is minimally controversial.

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This is a giant UK study of in the UK for no particular reason,

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they decided to look at thousands, hundreds of thousands of patients and do

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PFT's.

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So for no reason,
like a lot of them were done for no

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reason.

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And then comparing RA patients to general population. 

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So they have this big biobank where I think they were standardizing things.

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But anyway, over 300,000 patients RA, we're about 0.6%.

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So we think of RA as high as 1%.

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So 0.6% isn't so wrong.

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And again, 72% women,
it's about 80% in a lot of studies.

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So again quite accurate and about 3/4 being RF positive or a bit more.

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So what did they find?

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They found restrictive lung disease is more common in the RA patients than the

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general's very match population because it was a giant data set.

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So mild restrictive about a 1.34 odds,
a moderate about the same idea and severe

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about two fold increase.

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OK, we kind of know that.

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But obstructive was also increased, not mild but moderate or severe.

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And in other studies, including from BC database,

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the billing database, the BC,
they found that emphysema was increased

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in RA non-smokers about five times more than the general population of

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non-smokers even one to two years before they had their RA.

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So there's a lot we don't know about obstructive changes too.

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And the prevalence of ILD, you can see here it can vary,

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but in general and rheumatoid it's about 10% of rheumatoids,

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it's more but 10% being clinically relevant that we get our respirologists

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involved Scleroderma one in,
three to one in and you know to even 1

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and 2 will have ILD,
it's clinically relevant in at least 15% of

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those patients.

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Myositis, you can see the various odds.

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Lupus not very common, undifferentiated connective tissue

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disease, who knows.

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But if they look like Scleroderma-like they have a Scleroderma risk,

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if they look myositis-like they have a myositis risk.

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So we're back to the guy.

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So our guy is a smoker,
strongly positive RF and he had joint

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pains.

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He had this ILD picture certainly on chest X-ray and confirmed at least on

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the view we showed you on CT.

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So interestingly,
he's over 60 and he's had Raynaud's the

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last four years.

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So our antenna and rheumatology go up.

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If you get Raynaud's over the age of 50, we always wonder is there a secondary

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association?

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Whereas if you get it when you're 32, that's really common,

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and if you get it as a teen, it's really common.

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So no symptoms of inflammatory arthritis.

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His joint pains.

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He had worked in construction and he had what we call worker hand.

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He had osteoarthritis in his hands and he worked in construction just to know until

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retiring.

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And heaven knows what that means.

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On exposure of stuff that you're digging up and jackhammering and silica dust,

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etcetera.

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No past chest X-rays or PFTs.

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Well,
except for mild high blood pressure on

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treatment, no worrisome meds.

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So no nitrofurantoin or chemo with bleomycin or anything like that.

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He maybe had frequent pneumonia as a baby, but he's grasping at straws.

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When he was asked the question,
his aunt had RA or maybe OA and half of

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self report of RA and half of
family history report of RA isn't. Half is,

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but half isn't.

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So they double the the prevalence of RA if they make it up by saying yeah,

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"my aunt was like crippled up" and it could
have been a roast of OA.

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So we look at him,
no inflammatory arthritis,

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but he did have OA of his hand.

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He had bilateral basal crackles to the mid lungs bilaterally posteriorly normal

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vitals strongly positive RF.

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We didn't repeat it.

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We were just recording what he already had.

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Anti CCP was done because it might be relevant to this case with the RF because

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I'm just telling you that lungs sometimes predate the RA.

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So negative, anti CCP, ANA, moderate positive, interestingly,

00:13:55.954 --> 00:14:02.320
and so in ENA was done, the extractable nuclear antigens, and he was Ro positive.

00:14:02.520 --> 00:14:11.880
So if I was going to highlight Renaud's RF, Ro and ANA and having this ILD.

00:14:12.960 --> 00:14:14.440
So let's put the poll up.

00:14:14.440 --> 00:14:15.720
So what do you think this patient has?

00:14:15.720 --> 00:14:20.598
We can pull up right now. RA, UIP, IPAF or none of the above because I'm not really

00:14:20.598 --> 00:14:23.378
sure,
but let's vote and see what people say

00:14:23.378 --> 00:14:26.465
and we'll leave it up for maybe another few

00:14:26.465 --> 00:14:26.960
seconds.

00:14:28.040 --> 00:14:28.160
Yeah.

00:14:28.240 --> 00:14:29.880
So we got lots of people voting.

00:14:29.880 --> 00:14:35.200
And I mean, you know,
the title of our lecture is tonight.

00:14:35.200 --> 00:14:37.160
So OK, we'll end the poll.

00:14:37.160 --> 00:14:40.480
So 70% said IPAF and 10 and 10

00:14:40.480 --> 00:14:45.880
I thought it would be kind of split somehow. It says "failed to show the poll"

00:14:45.880 --> 00:14:48.000
Sorry I'm sharing but I didn't share.

00:14:48.120 --> 00:14:55.720
So 70% IPAF and about 10% of of UIP or RA and some people did a cop out.

00:14:55.720 --> 00:14:56.320
It's none of it.

00:14:56.320 --> 00:15:00.240
I think it's his,
his occupational exposure from silica

00:15:00.240 --> 00:15:03.600
dust, which you know, increases lots of things.

00:15:03.600 --> 00:15:06.120
So we, we might go there at some point.

00:15:06.360 --> 00:15:08.120
So oops, sorry.

00:15:08.400 --> 00:15:09.560
So just going back.

00:15:09.560 --> 00:15:13.160
So my questions to respirology for Daniel to help.

00:15:13.440 --> 00:15:16.353
So you know,
is this IPF if we get more cuts,

00:15:16.353 --> 00:15:18.760
do we have some honeycombing in there?

00:15:18.760 --> 00:15:20.360
Do I need it to be UIP?

00:15:20.360 --> 00:15:23.240
Well, I think of IPF having UIP of course.

00:15:23.480 --> 00:15:26.400
Is it RA-ILD or do you guys think it's IPAF?

00:15:26.680 --> 00:15:29.400
And then what, what should we follow?

00:15:29.400 --> 00:15:32.960
Like this guy did come to the emergency emergency room with symptoms.

00:15:32.960 --> 00:15:36.520
So do we follow his PFTs and HRCT?

00:15:36.520 --> 00:15:41.480
Do we just need PFTs because we know his CT is already not normal and how often?

00:15:41.480 --> 00:15:44.956
So Daniel,
I'm going to shift here the slide and

00:15:44.956 --> 00:15:50.073
send it to you to tell me what to do with this guy and to tell me what he has

00:15:50.073 --> 00:15:51.320
sounds good.

00:15:52.520 --> 00:15:55.328
We might not be much further ahead, but, but I'll give it a,

00:15:55.328 --> 00:15:56.480
I'll give it a shot here.

00:15:57.400 --> 00:16:00.995
And I,
I like to think about it in terms of ILD 

00:16:27.280 --> 00:16:30.680
And it's sort of what we call, quote un-quote, idiopathic.

00:16:30.680 --> 00:16:35.240
And anything is idiopathic if you don't understand it or if you don't look hard

00:16:35.240 --> 00:16:35.640
enough.

00:16:36.480 --> 00:16:39.287
And so if you go forward a couple of times, sorry,

00:16:39.287 --> 00:16:42.040
I have a couple of animations here on this slide.

00:16:43.400 --> 00:16:44.000
Sorry.

00:16:44.640 --> 00:16:47.520
Yeah, OK, let's try it again.

00:16:47.520 --> 00:16:51.320
Sometimes my clicking there we go others, yeah, yeah.

00:16:51.600 --> 00:16:55.782
So on one end of the spectrum if you have a clear underlying CTD,

00:16:55.782 --> 00:16:58.000
we'll we'll label that as a CTD-ILD.

00:16:58.200 --> 00:17:02.991
On the other end of the spectrum,
if you have for example a UIP pattern on

00:17:02.991 --> 00:17:08.357
imaging and we can't find a reason for it and especially if you're an older male ex

00:17:08.357 --> 00:17:11.360
smoker,
we've come up with a specific name for

00:17:11.360 --> 00:17:11.680
that.
00:17:11.960 --> 00:17:14.680
And the specific name for that is is IPF now.

00:17:15.000 --> 00:17:19.619
But if you have NSIP, for example, and you have no idea why it's there,

00:17:19.619 --> 00:17:23.340
you could just as easily label that with idiopathic NSIP,

00:17:23.340 --> 00:17:27.959
which is another diagnostic label that we have in our bucket of labels.

00:17:28.440 --> 00:17:31.200
But who's to say exactly what that is?

00:17:31.680 --> 00:17:36.974
And so somewhere in the middle of this is, is what has been defined as IPAF,

00:17:36.974 --> 00:17:40.571
where you have some kind of flavour of autoimmunity,

00:17:40.571 --> 00:17:45.798
some flavour of CTD features and maybe even some morphologic features on

00:17:45.798 --> 00:17:49.531
on CT scan or pathology to suggest something CTD like,

00:17:49.531 --> 00:17:53.400
but not quite enough to get us there to a bonafide CTD.

00:17:53.760 --> 00:17:58.393
And this this is something that was really developed as a research statement

00:17:58.393 --> 00:18:03.207
and probably mostly to get our foot in the door in order to be able to assign a

00:18:03.207 --> 00:18:07.600
label to this thing and then be able to study it and see where it falls.

00:18:07.600 --> 00:18:09.880
If it is it more similar to CTD to not?

00:18:09.880 --> 00:18:11.000
Is it a different entity?

00:18:11.240 --> 00:18:14.330
And, and we don't know yet, but starting with a definition is,

00:18:14.330 --> 00:18:18.156
is naming something is the first thing you always have to do before you to

00:18:18.156 --> 00:18:19.040
start to study it.

00:18:21.360 --> 00:18:26.878
And so IPAF interstitial pneumonia with autoimmune features, it's really the,

00:18:26.878 --> 00:18:32.326
the classification for it is that you have to have an interstitial pneumonia,

00:18:32.326 --> 00:18:35.400
you have to exclude alternative etiologies.

00:18:35.680 --> 00:18:39.561
And two and three on this slide are kind of the same thing because you don't meet

00:18:39.561 --> 00:18:40.840
criteria for a defined CTD.

00:18:40.840 --> 00:18:44.960
So that essentially kind of excludes that CTD-ILD nature of it.

00:18:45.760 --> 00:18:48.305
And then if you have all of these
features,

00:18:48.305 --> 00:18:52.644
then you look at 3 domains and you ideally want to have kind of two out of

00:18:52.644 --> 00:18:56.000
three of these clinical serologic or morphologic domains.

00:18:56.000 --> 00:18:57.840
And we'll talk a little bit about them.

00:18:58.760 --> 00:19:02.631
So on next slide,
here are some of the clinical,

00:19:02.631 --> 00:19:08.320
all the features I should say,
and you guys know this better than I do.

00:19:08.320 --> 00:19:13.062
And we as respirologists rely a ton on rheumatologists for looking at those

00:19:13.062 --> 00:19:18.054
clinical features and as well as perhaps annoyingly interpreting some serologic

00:19:18.054 --> 00:19:20.800
features when we send off a myositis panel.

00:19:20.800 --> 00:19:23.385
And,
and we might not have the best idea of

00:19:23.385 --> 00:19:27.439
what this means if you know,
X or Y is positive in the setting of no

00:19:27.439 --> 00:19:29.320
other kind of clinical symptoms.

00:19:30.040 --> 00:19:32.822
But all this is to highlight Raynaud's is a

00:19:32.822 --> 00:19:37.251
a pretty common one that shows up that would meet the criteria for a clinical

00:19:37.251 --> 00:19:38.160
feature up here.

00:19:39.120 --> 00:19:44.472
And then in terms of morphologic features, which is where I'd like to spend a little

00:19:44.472 --> 00:19:49.258
bit more of my time on and really on radiology because histopathology we're

00:19:49.258 --> 00:19:53.603
doing biopsies less and less,
but the morphologic features that were

00:19:53.603 --> 00:19:58.200
defined for this entity are really NSIP, OP or an overlap between the two.

00:19:58.960 --> 00:20:02.583
And you can look at that and you can say, hey, why isn't,

00:20:02.583 --> 00:20:05.520
why aren't other morphologic patterns on here?

00:20:05.720 --> 00:20:08.120
If you have UIP,
does this not make it IPAF?

00:20:08.120 --> 00:20:12.233
If you have a flavour of autoimmunity? if you have an airway centric pattern,

00:20:12.233 --> 00:20:14.080
does it not make it IPAF anymore?

00:20:14.840 --> 00:20:15.280
And.

00:20:16.120 --> 00:20:17.880
I,
I don't know what the right answer is to

00:20:17.880 --> 00:20:18.080
that.

00:20:18.080 --> 00:20:23.053
The reason why we define this using anchoring predominantly in an NSIP or an

00:20:23.053 --> 00:20:27.962
OP pattern is because these are the patterns that we know and seem to occur

00:20:27.962 --> 00:20:33.000
most commonly in some of the best studied ILD, like Scleroderma, for example.

00:20:33.640 --> 00:20:36.955
And, and because of that when we see NSIP,

00:20:36.955 --> 00:20:41.609
we tend to anchor towards, oh,
could there be an autoimmune disease here

00:20:41.609 --> 00:20:42.120
as well?

00:20:42.840 --> 00:20:45.760
And that's really the reason why it's on this list.

00:20:45.760 --> 00:20:48.280
And you fHP or airway centric disease isn't.

00:20:48.640 --> 00:20:52.958
So if you, if we go forward a little bit, just one, one comment went well,

00:20:52.958 --> 00:20:55.320
there's a question from the audience too.

00:20:55.320 --> 00:20:57.120
Two people are thinking the same way.

00:20:57.320 --> 00:21:01.520
And then before that just would it for the rest of the rheumatologist.

00:21:01.520 --> 00:21:03.560
What does OP stand for?

00:21:03.560 --> 00:21:04.960
For us, it's osteoporosis.

00:21:04.960 --> 00:21:07.360
So we know it's not fair enough.

00:21:07.360 --> 00:21:07.920
Fair enough.

00:21:07.920 --> 00:21:10.065
No,
you wouldn't want me diagnosing

00:21:10.065 --> 00:21:10.840
osteoporosis.

00:21:11.480 --> 00:21:13.360
OP would be organizing pneumonia.

00:21:14.240 --> 00:21:17.400
NSIP here would be non specific interstitial pneumonia.

00:21:18.280 --> 00:21:22.676
The non specific interstitial pneumonia is a little bit of a misnomer in the

00:21:22.676 --> 00:21:27.243
sense that it it tends to have a fairly specific look on it on radiology and

00:21:27.243 --> 00:21:30.840
in terms of being basal predominant, having more ground glass.

00:21:30.840 --> 00:21:34.729
And in about 1/4 of cases,
there's this entity of subpleural sparing

00:21:34.729 --> 00:21:39.240
where just along the edge of the pleura, the disease gets milder or disappears.

00:21:39.720 --> 00:21:42.893
And,
and that really gives you a sense of what

00:21:42.893 --> 00:21:48.091
we classically define as NSIP. Organizing pneumonia is really just defined by

00:21:48.091 --> 00:21:53.019
consolidation and ground glass and, and really what's called perilobular

00:21:53.019 --> 00:21:53.560
sparing.

00:21:53.560 --> 00:21:57.806
So you'll see 1 little lobule of the lung that looks normal and right beside it,

00:21:57.806 --> 00:22:00.480
another one that's kind of consolidated and white.

00:22:01.120 --> 00:22:04.720
And, and that's what radiologists, that's, that's the whole magic of OP.

00:22:05.360 --> 00:22:09.424
That's what radiologists look to see to say, "hey, this,

00:22:09.424 --> 00:22:14.723
looks like OP" and for for the older rheumatologists in the gang, COP

00:22:14.723 --> 00:22:20.240
cryptogenic organizing pneumonitis or pneumonia; formerly known as BOOP.

00:22:20.440 --> 00:22:21.520
That's what we're talking about.

00:22:21.720 --> 00:22:22.920
Just to know.

00:22:23.080 --> 00:22:26.150
So the audience is kind of implying, well, you know,

00:22:26.150 --> 00:22:28.120
this guy had Reynolds older onset.

00:22:28.120 --> 00:22:30.400
Did he not like what about myositis panel?

00:22:30.400 --> 00:22:33.520
So the question is, so I didn't order.

00:22:33.520 --> 00:22:36.450
This is a fake case,
but I've had people like this is based on

00:22:36.450 --> 00:22:37.520
real people by the way.

00:22:55.000 --> 00:22:59.640
Stay tuned for more cases maybe,
but we didn't, like his CK wasn't done.

00:22:59.640 --> 00:23:02.990
His power was fine and probably eventually his CK was done,

00:23:02.990 --> 00:23:07.123
but it probably wouldn't have changed what we were thinking at this point

00:23:07.123 --> 00:23:11.200
because clinically he did not not have inflammatory myositis.

00:23:11.480 --> 00:23:13.912
And you know,
they're kind of pesky antibodies,

00:23:13.912 --> 00:23:17.866
these myositis panel because I think every week there's a new one and I don't

00:23:17.866 --> 00:23:19.639
know how to interpret lots of them. 

00:23:19.880 --> 00:23:22.609
So I didn't,
I didn't think it would matter with the

00:23:22.609 --> 00:23:26.730
strongly positive his ANA meets it and his RF meets it and we didn't clinically

00:23:26.730 --> 00:23:27.399
see myositis.

00:23:27.400 --> 00:23:28.600
But it's a really good question.

00:23:28.800 --> 00:23:32.630
And Daniel, if you had said,
can you guys look harder to tell us what

00:23:32.630 --> 00:23:35.311
he really has because it might affect treatment,

00:23:35.311 --> 00:23:39.360
then we would have probably gone on to do like say a double stranded DNA.

00:23:39.520 --> 00:23:42.360
But we didn't think he had lupus, a myositis panel, etcetera.

00:23:42.560 --> 00:23:45.080
But it's good 2 people in the audience picked it up right away.

00:23:45.080 --> 00:23:46.840
So good for them.

00:23:47.000 --> 00:23:50.371
But if you like, we don't usually witch hunt too much,

00:23:50.371 --> 00:23:53.120
but we will do it because it could affect
treatment.

00:23:53.280 --> 00:23:56.705
And now that we prioritize different treatments and different diseases,

00:23:56.705 --> 00:23:57.800
it might affect it too.

00:23:58.840 --> 00:24:00.120
So thanks for that.

00:24:00.120 --> 00:24:03.000
I'm just trying to move on somewhere.

00:24:03.240 --> 00:24:05.880
My cursor is Oh yeah, sorry.

00:24:06.280 --> 00:24:07.040
Yes, yeah.

00:24:07.400 --> 00:24:11.212
So this is as I was saying,
why not other patterns here and just

00:24:11.212 --> 00:24:15.611
because we have more experience with the prevalence of NSIP and autoimmune

00:24:15.611 --> 00:24:17.840
flavored or CTD-ILD kind of phenotypes.

00:24:18.120 --> 00:24:21.840
If you go over to the next slide, we'll see a little bit why.

00:24:21.840 --> 00:24:27.689
So this was part of a meta analysis that looked at CTD-ILD specifically and looked

00:24:27.689 --> 00:24:33.040
at different patterns that come out in
these different subtypes of of CTD.

00:24:33.680 --> 00:24:37.960
And you can see in rheumatoid arthritis about 50/50 be between UIP and NSIP.

00:24:38.920 --> 00:24:41.775
In Scleroderma,
the majority of cases are going to be

00:24:41.775 --> 00:24:42.040
NSIP.

00:24:42.840 --> 00:24:46.353
In myositis,
you'll see this overlap between NSIP and

00:24:46.353 --> 00:24:47.720
organizing pneumonia.

00:24:48.360 --> 00:24:52.725
So really Scleroderma,
which really forms the crux of our

00:24:52.725 --> 00:24:56.037
evidence in CTD-ILD and myositis especially,

00:24:56.037 --> 00:25:01.833
it's more of this kind of what we think is more inflammatory NSIP kind of OP
00:25:01.833 --> 00:25:02.360
flavor.

00:25:03.080 --> 00:25:05.600
And then you have a, a smattering of, of other things.

00:25:05.600 --> 00:25:10.394
But really our confidence in something that's autoimmune flavoured is,

00:25:10.394 --> 00:25:14.379
is geared a lot in NSIP,
which is why when this statement,

00:25:14.379 --> 00:25:18.026
this research statement defining IPAF was developed,

00:25:18.026 --> 00:25:22.686
they really wanted kind of to see NSIP from a morphologic domain to,

00:25:22.686 --> 00:25:25.319
to give it points towards autoimmunity.

00:25:25.600 --> 00:25:29.106
But as as I said before, I would argue, does that mean that if you have a UIP

00:25:29.106 --> 00:25:31.399
pattern it,
it shouldn't qualify and you shouldn't

00:25:31.399 --> 00:25:34.680
treat it that way if you have a,
a positive RF and kind of the same case

00:25:34.680 --> 00:25:35.400
in front of you?

00:25:35.840 --> 00:25:38.570
I don't know, I would err towards the side of saying no

00:25:38.570 --> 00:25:41.080
that still probably we should think about that as IPAF.

00:25:41.800 --> 00:25:45.404
And maybe I'm a little bit ahead of the game in that thinking,

00:25:45.404 --> 00:25:49.696
but our research statement and our research definition hasn't quite caught

00:25:49.696 --> 00:25:50.440
up with that.

00:25:51.400 --> 00:25:54.160
If we go forward one more slide here.

00:25:56.080 --> 00:25:56.240
Yeah.

00:25:56.600 --> 00:26:00.473
So this is some of our own data from from the Canadian Registry for Pulmonary

00:26:00.473 --> 00:26:00.920
Fibrosis.

00:26:00.920 --> 00:26:02.840
And there's,
there's a lot of stuff on this slide.

00:26:02.840 --> 00:26:07.847
But basically all of this is to say we we looked at about 1600 patients where we

00:26:07.847 --> 00:26:12.854
had a chest radiologist go through their imaging at presentation and really hone

00:26:12.854 --> 00:26:16.439
down on what the pattern of their imaging is at the time.

00:26:16.840 --> 00:26:22.254
And contrary to the last slide where we really looked at UIP and NSIP and OP,

00:26:22.254 --> 00:26:27.600
there's sort of been a new kind of pattern on the block that's been defined.

00:26:27.600 --> 00:26:30.209
It it, it's not actually new, but just the,

00:26:30.209 --> 00:26:35.012
the word for it or the definition for it came with a new guideline that that was

00:26:35.012 --> 00:26:36.080
published in 2021.

00:26:36.320 --> 00:26:41.015
And that's what we call an FHP like pattern and a fibrotic hypersensitivity

00:26:41.015 --> 00:26:42.560
pneumonitis like pattern.

00:26:43.080 --> 00:26:46.680
All of that is to say that pattern is supposed to be more airway centric.

00:26:46.920 --> 00:26:48.880
So you're supposed to have more airways disease.

00:26:48.880 --> 00:26:53.080
So UIP had its kind of set of basal predominant fibrosis.

00:26:53.400 --> 00:26:56.436
NSIP looked a little bit more ground glassy,

00:26:56.436 --> 00:27:01.835
but still basal predominant and this FHP or airway centric pattern really shows

00:27:01.835 --> 00:27:03.320
areas of air trapping.

00:27:03.320 --> 00:27:07.643
And as we saw from the previous slide, a lot of these CTD patients can present

00:27:07.643 --> 00:27:11.966
with obstructive airways disease as well and we don't understand that quite as

00:27:11.966 --> 00:27:12.240
well.

00:27:12.960 --> 00:27:16.494
But now again we're defining more and segmenting more and more of these

00:27:16.494 --> 00:27:18.680
patterns to try to get a better understanding.

00:27:18.960 --> 00:27:24.229
And I've included this slide just to say that there is a ton of patients with

00:27:24.229 --> 00:27:29.499
CTD-ILD or with IPAF that you see in the green that have not only typical UIP

00:27:29.499 --> 00:27:33.890
patterns that you see in the first kind of two bars on the left,

00:27:33.890 --> 00:27:39.025
but also in the last two second to last two bars on the right where it says

00:27:39.025 --> 00:27:41.119
compatible FHP and typical FHP.

00:27:41.120 --> 00:27:45.439
So these are airway centered type of patterns where you see gas trapping and

00:27:45.439 --> 00:27:49.926
mosaic attenuation and there's a ton of patients that present with this kind of

00:27:49.926 --> 00:27:50.880
appearance on CT.

00:27:51.520 --> 00:27:55.974
So all of this is to bring it back to the point that, you know, is NSIP and OP,

00:27:55.974 --> 00:27:59.760
are those the only patterns that are going to lead us towards IPAF?

00:28:00.000 --> 00:28:04.636
If you go by the strict letter of the law of what was published in, you know,

00:28:04.636 --> 00:28:08.481
in 2015, then yes,
you would have to say it has to be only

00:28:08.481 --> 00:28:09.160
NSIP and OP.

00:28:09.560 --> 00:28:14.134
And I would say that more and more we're finding out that CTD-ILD can present in

00:28:14.134 --> 00:28:17.964
other ways as well with UIP, especially in RA or with airway centric

00:28:17.964 --> 00:28:19.680
disease and a bunch of CTD-ILD.

00:28:19.680 --> 00:28:23.322
And maybe that should also qualify you as
IPAF or at least in my mind,

00:28:23.322 --> 00:28:26.560
I still think of it as being potentially compatible with IPAF.

00:28:33.960 --> 00:28:37.000
So people are getting older with some of these diagnosis.

00:28:37.200 --> 00:28:42.679
We think of IPF as older guys in general, but even our connective tissue disease

00:28:42.679 --> 00:28:47.280
age of onset is going up overtime as our general population is too.

00:28:47.520 --> 00:28:51.177
And I think we're seeing more mixed bags because they might have some old things

00:28:51.177 --> 00:28:52.080
that we didn't, like

00:28:52.080 --> 00:28:55.790
no one did a chest X-ray when something else was going on and we're seeing

00:28:55.790 --> 00:28:58.213
restrictive,
obstructive and then and trying to,

00:28:58.213 --> 00:29:00.440
you know,
who treats what and what do we do?

00:29:00.520 --> 00:29:01.680
So just a comment.

00:29:01.680 --> 00:29:04.960
I agree it's quite,
it's getting more complicated.

00:29:05.160 --> 00:29:09.708
We want a really good radiologist and we want the respirologist like now every

00:29:09.708 --> 00:29:14.544
respirologist certainly that does general resp and then specialty rest knows how to

00:29:14.544 --> 00:29:15.120
treat IPF.

00:29:15.120 --> 00:29:18.097
So that helps us for them to say it's not that or it is,

00:29:18.097 --> 00:29:21.859
but there's a question that came up and I think it's good in this case,

00:29:21.859 --> 00:29:24.680
it'll probably be relevant to the other case as well.

00:29:24.880 --> 00:29:31.146
So if someone has an RNP, sometimes our ENA just says "up to

00:29:31.146 --> 00:29:34.280
0.8 is negative, 1 is positive, 2 is more positive.

00:29:34.280 --> 00:29:35.440
But we they don't go up.

00:29:35.440 --> 00:29:37.240
We don't know that it's strongly positive.

00:29:37.240 --> 00:29:39.040
Like they don't go to 16 or anything.

00:29:39.240 --> 00:29:44.960
So some of these ENAs
don't tell us how positive it is.

00:29:44.960 --> 00:29:49.660
And a question is, you know,
if I have a person with an RNP that's

00:29:49.660 --> 00:29:52.280
a 2 and less than 0.8 is a negative.

00:29:52.280 --> 00:29:56.297
So it's a bit, it's like double, maybe, maybe double to triple the upper limit of

00:29:56.297 --> 00:29:56.640
normal.

00:29:57.160 --> 00:30:00.556
Do we, you know,
are we supposed to tell you the RNP is

00:30:00.556 --> 00:30:02.800
irrelevant if we can't find anything?

00:30:02.920 --> 00:30:06.295
Or are we supposed to just say you want us to use a drug and we'll do it because

00:30:06.295 --> 00:30:07.920
we know how to get the drugs sometimes?

00:30:08.120 --> 00:30:10.080
So it is, it's a valid question.

00:30:10.080 --> 00:30:12.645
And Daniel,
I don't know if you have an easy answer

00:30:12.645 --> 00:30:13.040
to that.

00:30:14.520 --> 00:30:17.954
I would this,
this starts to get on that spectrum of

00:30:17.954 --> 00:30:19.640
kind of of of probability.

00:30:19.640 --> 00:30:24.696
And I would say that the same way I I've just talked about kind of the morphology,

00:30:24.696 --> 00:30:29.022
the that NSIP-OP pattern being more indicative or perhaps more strongly

00:30:29.022 --> 00:30:32.800
anchored in our minds to something with an autoimmune flavor.

00:30:33.000 --> 00:30:38.248
So if you have a borderline serology like that with something that's really NSIP-OP

00:30:38.248 --> 00:30:41.283
looking, I'm more leaning towards, for example,

00:30:41.283 --> 00:30:44.382
more often calling that IPAF and saying, yeah,

00:30:44.382 --> 00:30:49.251
that probably is significant If if you have something that looks not like an

00:30:49.251 --> 00:30:53.235
NSIP-OP, if you have, you know, UIP and an older male smoker

00:30:53.235 --> 00:30:56.460
otherwise, and really nothing else to speak up for

00:30:56.460 --> 00:31:00.824
CTD except that that RNP, I might be leaning more towards calling that

00:31:00.824 --> 00:31:03.479
something different and ignoring that.

00:31:04.040 --> 00:31:10.407
So that the the other features in this table basically kind of point me towards

00:31:10.407 --> 00:31:11.920
one way or another.

00:31:12.360 --> 00:31:16.632
If the other features in the clinical and morphologic domains are are strongly

00:31:16.632 --> 00:31:20.040
rooting me towards IPAF,
I'm comfortable going towards there.

00:31:20.240 --> 00:31:23.472
If if they don't,
then then maybe it's easier to ignore

00:31:23.472 --> 00:31:24.800
that serologic feature.

00:31:26.560 --> 00:31:30.120
So it's putting all our our brains together and trying to decide.

00:31:30.120 --> 00:31:36.720
So Reynaud's strongly positive RF, ANA
and this Ro, he's an NSIP.

00:31:37.840 --> 00:31:39.800
So we couldn't call him RA.

00:31:40.320 --> 00:31:42.400
And we sent them to Daniel.

00:31:42.400 --> 00:31:45.280
And you said, well, yeah, I think he's IPAF.

00:31:46.560 --> 00:31:51.378
So my next question was, you know, when do we treat? this guy was short of

00:31:51.378 --> 00:31:51.800
breath.

00:31:52.240 --> 00:31:55.120
I haven't given the PFTs because who knows what they are.

00:31:55.120 --> 00:31:57.160
We we, you know,
they're ordered kind of thing.

00:31:57.320 --> 00:31:58.320
We know the CT.

00:31:58.480 --> 00:32:02.320
So I guess helping us when, how much do we order?

00:32:02.320 --> 00:32:04.960
What do you guys order and when do we trigger treatment?

00:32:05.840 --> 00:32:07.600
Daniel, that's a loaded question.

00:32:08.480 --> 00:32:12.496
Yeah, I, I think I'll,
I'll say maybe a couple of words on,

00:32:12.496 --> 00:32:15.040
on follow up of ILD in this slide.

00:32:15.040 --> 00:32:16.727
And then,
and then we'll get a little bit to

00:32:16.727 --> 00:32:18.752
treatment and,
and we'll kind of go a little bit back

00:32:18.752 --> 00:32:19.840
and forth between us I think.

00:32:19.840 --> 00:32:23.774
And I'll maybe leave you with a bit of an ILD physicians kind of

00:32:23.774 --> 00:32:27.146
approach to treatment or,
or my kind of general overview of how I

00:32:27.146 --> 00:32:27.760
think of it.

00:32:28.440 --> 00:32:33.433
But in terms of follow up and, and this is really in line with

00:32:33.433 --> 00:32:36.586
the recent ACR guidelines for SARD,

00:32:36.586 --> 00:32:39.872
which again,
most of our evidence and most of our

00:32:39.872 --> 00:32:42.960
thinking around IPAF is, is taken from CTD-ILD.

00:32:43.840 --> 00:32:47.131
But in,
in all ILD we always follow these three

00:32:47.131 --> 00:32:47.680
domains.

00:32:47.680 --> 00:32:53.446
We always follow clinical sympomatology,
what PFTs are doing and it's really FVC

00:32:53.446 --> 00:32:58.215
and DLCO. DLCO I should mention and this may be helpful is that,

00:32:58.215 --> 00:33:00.280
but it can be quite variable.

00:33:00.840 --> 00:33:05.480
It can vary by as much as 10 to 15% predicted from visit to visit.

00:33:05.680 --> 00:33:10.080
So it's one of those where if you go from 70 to 60, I don't know, do I believe it?

00:33:10.080 --> 00:33:11.200
Do I just repeat it?

00:33:11.200 --> 00:33:11.920
Is that true?

00:33:11.920 --> 00:33:13.040
Are we worsening? I'm not sure.

00:33:13.360 --> 00:33:15.520
FVC should be a lot more reliable.

00:33:15.520 --> 00:33:18.424
And usually if you have a worsening of 5% or greater,