Advanced diagnostic testing in Interstitial Lung Disease (ILD)

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Alright,
welcome everyone and welcome to this talk.

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So we're going to be talking about an advanced diagnostic testing today and

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trustitional lung disease.

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My name is Stacy Lok.

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I'll be your moderator tonight and it's my pleasure to introduce our speaker.

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I am an assistant professor at the University of Saskatchewan and also a

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specialist in ILD.

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My colleague here, Doctor Jolene Fisher, is a research director at the University

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of - Sorry,
a director of interstitial lung disease

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program at the University Health Network and an assistant professor at the

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University of Toronto.

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She's received her Doctor of Medicine and Internal Medicine residency training

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program from the University of Manitoba.

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She then completed a respirology residency and interstitial lung disease

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fellowship and a Masters of Science in clinical Epidemiology and Healthcare

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research at the University of Toronto.

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Her research interests include interstitial lung disease, health service

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research,
registries and outcomes research.

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So tonight,
we hope that you find value in tonight's

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unaccredited medical education presentation.

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Before we start,
we want to cover a few housekeeping items

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for the next slide.

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Here,
we ask that you provide us with feedback

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at the conclusion of the event by completing the sessions evaluation.

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We'll be posting the evaluation link in the chat box at the end of tonight's
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presentation prior to the Q and A portion of this event.
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We truly appreciate you taking the time to provide feedback because it helps us
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programs that provide value. To ensure the best possible sound quality for everyone
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attending.
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We note that all participant lines will remain unmuted or sorry,
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muted throughout the program.
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If you have any questions,
please type into the chat box at any time.
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This presentation is being recorded and
will be made available with slides after
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this evening's program.
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It is also important to note that this program has received financial support
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from Boehringer Ingelheim.
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The faculty has received an honorarium for their participation.
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In the spirit of balance and integrity, there are sorry,
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this evening's program is fair and balanced and the faculty has been fully
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responsible for developing all content of this learning activity and the spirit,
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spirit of balance and integrity.
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There's a few of the faculty's disclosures attached on the next slide.
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And now it's my pleasure to pass things over to Doctor Jolene Fisher.
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Thank you.
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And then lastly,
take a look at some of the emerging and
1d147959-5908-46a8-86e5-e3c80048c707-1

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future ILD diagnostics.
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There's quite a bit,
it's I think a really exciting and
0ebe4074-0d59-44cb-879a-177255e13d47-1

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evolving active area,
but I want to spend a bit of time
0ebe4074-0d59-44cb-879a-177255e13d47-2

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focusing specifically on endobronchial optical coherence tomography or EBOCT as
0ebe4074-0d59-44cb-879a-177255e13d47-3

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well as a few others.
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All right, so let's start with the case.
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So this is a 70 year old man who presented to clinic with a several month
24081b42-1d86-4a5f-aadf-ed1690a0390f-1 

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history of cough and exertional shortness of breath.
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Really had no relevant past medical history, so never smoker, no medications.
bef38a8d-c218-4ee0-90c8-e0bd733ca2a4-0 

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Extensive review of systems for connective tissue disease symptoms was
bef38a8d-c218-4ee0-90c8-e0bd733ca2a4-1 

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negative.
af19de95-0b9a-43dc-b426-e2feff4d6539-0 

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No organic or inorganic exposures could be identified.
db20c8d3-eaab-4715-a6a4-ae6d42f37ded-0 

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Had no family history of connective tissue disease or ILD,
db20c8d3-eaab-4715-a6a4-ae6d42f37ded-1 

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and extensive serologic testing for an autoimmune disease was negative.
63d3b1f4-28ba-498b-808b-114dc54a80da-0 

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And so this was the CT scan.
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So just a screenshot of an axial image and you can see here hopefully that there
15fc2cba-77e1-40a9-ae65-c2bc02c2091a-1 

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is some ground glass opacity that's quite diffuse.
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There is some mosaic attenuation.
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So there's areas of whiter lung next to areas of darker lung.
786dbb84-4384-4660-99cd-cb1a0e96bb6b-0 

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And there is what we would consider the three density signs.
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So there's areas of black lung, what would be in keeping with air
35f8d1b6-30df-4686-8cc4-428597cbc5ab-1 

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trapping.
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There's areas of increased density and keeping with ground glass opacity.
e752342d-9d75-40ef-ac3d-339c2d01ba35-0 

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And then there's some areas of normal lung.
a9743ab9-294e-41ef-aa07-73d6b62bc938-0

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I'm not showing the expiratory images here,
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but there was evidence of gas trapping.
8794748e-ef5d-43ed-8625-36eefbabc966-0 

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There's no clear fibrosis.
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And if you were to scroll through all the images, which you're not going to do,
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So I'm just going to tell you it was quite a diffuse pattern with no real
09e3b997-da07-470b-892a-082fa9e79270-1

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zonal predominance.
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All right,
so I have a polling question for you.
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What would you do next?
2358fcb7-6382-4f95-97f4-6718db37263d-0

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A dart steroids B perform bronchoscopy for microbiology,
2358fcb7-6382-4f95-97f4-6718db37263d-1

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cell count and differential.
27b987c6-58e2-4910-a0cb-b9ff38c6f63b-0 

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C cryobiopsy or D surgical lung biopsy.
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Just give everyone a little bit of time to vote.
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All right,
Why don't we end it there and show the
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results?
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So these results should be showing up for you and hopefully you can see that about
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3/4 of the participants suggested bronchoscopy with BAL for microbiology
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cell counting differential and then a quarter suggested just forget it.
592b6ff2-efb1-47dd-8632-e789f8b56ad1-0 

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I'm pragmatic, let's start the steroids.
269a8fa3-17ab-4396-9ec3-8d65a635d264-0

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And then nobody suggested cryobiopsy or surgical lung biopsy.
bbf9d3c1-f8f8-481a-b92f-27d095ba4a55-0 

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All right,
So when do we consider advanced
bbf9d3c1-f8f8-481a-b92f-27d095ba4a55-1 

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diagnostic testing in our patients with
ILD?
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This figure is from the more recent ATS-IPF diagnostic guidelines.
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And I think most of you probably will recognize it,
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but I want to spend just a little bit of time going through it.
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So when we're thinking about a patient that might have IPF, as you know,
d3a33662-7394-43aa-8341-2e7e2932a51c-1 

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we do you know an extensive work up for a potential cause or associated condition
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such as extensive exposure history, autoimmune serology.
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Obviously if we find a diagnosis an underlying condition,
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then it's not going to be IPF.
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If we don't find anything,
we're spending a lot of time looking at
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that CT pattern and trying to characterize it into a UIP, probable UIP,
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indeterminate for UIP or most in keeping
with an alternate diagnosis.
78f65efd-be82-4f19-afbc-e0e4f5b2d186-0 

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And if available,
we're discussing these cases at an MDD.
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And if it is indeterminate for UIP or in keeping with an alternate diagnosis,
74779cd7-852e-44c7-beca-639408d5f151-1

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those are really the patients that we're thinking about doing advanced diagnostic
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testing,
whether it is just BAL with cell counted
74779cd7-852e-44c7-beca-639408d5f151-3

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differential, transbronchial lung cryobiopsy or surgical lung biopsy.
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And this panel here shows a figure from the hypersensitivity pneumonitis
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guidelines.
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So if we're looking at it from an HP lens, so we have a patient with newly detected
a6f4a061-f629-4cc7-ae1d-426cf503c43e-1 

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interstitial lung abnormalities on a CT chest and we're thinking could this be HP?
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We're doing that extensive exposure, exposure assessment.
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We're looking at that CT scan and really
they recommend BAL with lymphocyte
93b3e1cd-feeb-4704-b7a7-dda710b5b7c4-1 

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cellular analysis plus or minus a transbronchial biopsy earlier on in the
93b3e1cd-feeb-4704-b7a7-dda710b5b7c4-2 

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the diagnostic algorithm.
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And then if you,
if you do have someone that has a typical
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CT pattern,
typical exposure and lymphocytosis,
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often you can make a high diagnosis, high confidence diagnosis of HP.
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But if after all that,
the diagnosis is still unclear, you know,
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that's when you're really looking at transbronchial lung cryobiopsy or
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surgical lung biopsy.
6e1f9f2d-ae17-4397-8a30-8f9a80f2501d-0

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All right, so when to consider BAL?
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So really you should be thinking about BAL when you want to rule out infection,
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when you want to obtain cell count and
differentials.
7fa341b9-a10b-4228-8471-becefd589801-0

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So looking for lymphocytosis is helpful for distinguishing hypersensitivity
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pneumonitis from IPF or sarcoidosis.
d3054d33-c40e-49ec-b1f8-7e5f8e68e12b-0 

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In certain cases,
a high eosinophil count can suggest
d3054d33-c40e-49ec-b1f8-7e5f8e68e12b-1 

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eosinophilic pneumonia, for example.
a9873308-b41b-4296-adfa-2ac8caab6702-0 

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And when you look specifically at trying to distinguish fibrotic HP from IPF, BAL
a9873308-b41b-4296-adfa-2ac8caab6702-1 

00:10:01.453 --> 00:10:05.218
fluid,
lymphocyte thresholds of 20%, 30% and
40%
a9873308-b41b-4296-adfa-2ac8caab6702-2 

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will have sensitivities of 69%, 55% and 41%respectively,
a9873308-b41b-4296-adfa-2ac8caab6702-3 

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and then specificities of 61%, 80% and 93%.
c74533db-94fe-414a-9542-23ae433c5577-0 

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So, you know,
obviously the higher the lymphocyte
c74533db-94fe-414a-9542-23ae433c5577-1 

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thresholds, the better the specificity, but the worse the sensitivity.
ebd55cfc-e5a2-4de5-abf2-2aeb70d76eba-0 

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So what do the guidelines say that you should do?
2e62b610-a784-47f1-88b7-f7e99c8055c0-0

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The HP guidelines say that for patients with newly identified ILD where the
2e62b610-a784-47f1-88b7-f7e99c8055c0-1

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differential diagnosis includes non fibrotic HP,
2e62b610-a784-47f1-88b7-f7e99c8055c0-2

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the guideline committee recommends BAL with lymphocyte cellular analysis.
e692961b-4156-4e2a-8c3b-f9775164ae6e-0 

00:10:44.240 --> 00:10:49.064
And then for patients where the differential diagnosis includes fibrotic
e692961b-4156-4e2a-8c3b-f9775164ae6e-1 

00:10:49.064 --> 00:10:51.443
HP,
the guidelines suggest BAL with
e692961b-4156-4e2a-8c3b-f9775164ae6e-2 

00:10:51.443 --> 00:10:53.359
lymphocyte cellular analysis.
3fe0f766-1b4e-4ae1-82dd-ad34f4547ac4-0 

00:10:53.360 --> 00:10:59.643
So just to remind you,
recommending basically means that in most
3fe0f766-1b4e-4ae1-82dd-ad34f4547ac4-1 

00:10:59.643 --> 00:11:02.640
cases you would probably do it.
98d94969-8f98-4221-b7a4-4e8dcc4b750a-0

00:11:02.680 --> 00:11:06.716
Suggesting means that you know, it's, if somebody didn't do it,
98d94969-8f98-4221-b7a4-4e8dcc4b750a-1

00:11:06.716 --> 00:11:09.240
you wouldn't think that they were crazy.
3705e49a-a31b-4570-9a68-e797c8695634-0

00:11:12.400 --> 00:11:17.960
And then for IPF,
the guidelines suggested performing BAL
bbfae4f9-b4e0-4b28-95b4-45fd5641622e-0 

00:11:17.960 --> 00:11:21.880
This was a conditional suggestion, so pretty soft for patients with
bbfae4f9-b4e0-4b28-95b4-45fd5641622e-1 

00:11:21.880 --> 00:11:26.376
indeterminate and alternative and then probable with with an* which basically
bbfae4f9-b4e0-4b28-95b4-45fd5641622e-2 

00:11:26.376 --> 00:11:29.720
means many of them you know, it's probably not necessary.
6f1d7c1b-43bd-401a-bf05-7142d65d566f-0 

00:11:30.200 --> 00:11:33.833
And then in patients who have a UIP-CT pattern,
6f1d7c1b-43bd-401a-bf05-7142d65d566f-1 

00:11:33.833 --> 00:11:37.080
the recommendation was not to perform BAL.
f8c31c0b-bafe-45e5-a4f7-300422510385-0 

00:11:40.840 --> 00:11:44.120
So what do I do really?
3960f8f9-5c64-40b0-bfdd-73eb7855958c-0

00:11:44.120 --> 00:11:46.880
I perform BAL if infection is possible.
e991fb2f-0ee7-4b7a-919e-cff880204d60-0 

00:11:46.880 --> 00:11:49.640
So that really would include most non fibrotic HP.
bcf56dad-d581-4e4b-a21e-c00aed745f89-0 

00:11:49.640 --> 00:11:56.004
So I also would have done a BAL in this patient who ended up having non fibrotic
bcf56dad-d581-4e4b-a21e-c00aed745f89-1 

00:11:56.004 --> 00:11:56.240
HP.
5ef4192d-5e00-4305-8947-24113c8a68e2-0

00:11:57.840 --> 00:12:03.275
And then I would consider it in patients with an indeterminant or alternative for
5ef4192d-5e00-4305-8947-24113c8a68e2-1

00:12:03.275 --> 00:12:07.120
UIP-CT pattern if there's really no other clear diagnosis.
af393a26-d578-419c-94d6-11195aa00f75-0 

00:12:07.120 --> 00:12:09.560
And I think it has the potential to change, change my management.
9301cfb8-0106-4374-8297-06e4cb03f5a5-0

00:12:09.560 --> 00:12:12.480
So I'm definitely a pragmatist.
7143d990-2e2d-481c-91af-999f53a431e9-0

00:12:12.480 --> 00:12:14.800
I always think,
is this going to change management?
56b247bc-433b-47e1-bc3c-7ccc51905fc4-0 

00:12:16.080 --> 00:12:21.265
And then if I'm thinking about fibrotic HP, I do consider BAL, but I don't,
56b247bc-433b-47e1-bc3c-7ccc51905fc4-1 

00:12:21.265 --> 00:12:26.240
I wouldn't end up doing it universally on all my fibrotic HP patients.
fd712468-dee9-4df5-9e36-256c24bfc1e3-0 

00:12:26.240 --> 00:12:28.680
Although if you do do that,

I certainly think it's reasonable.
703daa0e-3e8b-4d73-9d82-7a0fbca47180-0 

00:12:30.040 --> 00:12:31.160
Again, you know it.
79dfdede-e56b-48f4-9e22-9c99e5699d47-0 

00:12:31.440 --> 00:12:35.007
It depends on whether or not I what else I think might be in the differential,
79dfdede-e56b-48f4-9e22-9c99e5699d47-1 

00:12:35.007 --> 00:12:38.440
and whether or not the result is really going to help me change management.
7aa2216f-2b46-4254-94b1-fc3de269dbd5-0 

00:12:45.080 --> 00:12:49.160
All right, so let's move on to case 2.5ca0a29d-54aa-4cb2-89ce-2ba7522c9168-0 

00:12:49.320 --> 00:12:54.597
So the reason for this patient's referral was whether or not she should have a
5ca0a29d-54aa-4cb2-89ce-2ba7522c9168-1 

00:12:54.597 --> 00:12:56.000
surgical lung biopsy. 
0bff4d63-9522-41ca-8427-8e83c2e94fc1-0

00:12:56.000 --> 00:13:00.901
And so this was a 55 year old female who presented with two years of shortness of
0bff4d63-9522-41ca-8427-8e83c2e94fc1-1

00:13:00.901 --> 00:13:01.320
breath.
4c3fc749-bb90-4e00-b0ec-3282a46cd471-0 

00:13:01.600 --> 00:13:05.840
She also had really no significant exposures.
63dae806-e808-4d9f-8d41-68db76356426-0

00:13:05.840 --> 00:13:09.760
She had no family history,
nothing up for connective tissue disease.
10d29c7f-969a-483c-955f-7cf6e97537b3-0

00:13:10.480 --> 00:13:15.200
Her CT which is here showed some ground glass opacity.
651b48ed-251a-4601-8d67-1e695295bf9e-0

00:13:15.680 --> 00:13:20.603
There was areas of fibrosis with some traction bronchiectasis and traction
651b48ed-251a-4601-8d67-1e695295bf9e-1

00:13:20.603 --> 00:13:21.720
bronchiolectasis.
7a107178-e46a-4e58-95d8-3748aa10ea5e-0

00:13:21.720 --> 00:13:26.886
There was, you know,
basal predominance but also some mid lung
7a107178-e46a-4e58-95d8-3748aa10ea5e-1

00:13:26.886 --> 00:13:28.280
zone involvement.
54ad07ad-5c5a-4b68-ba96-7bd6e2cf1688-0 

00:13:28.760 --> 00:13:33.682
It was para bronchovascular plus subpleural and the overall interpretation
54ad07ad-5c5a-4b68-ba96-7bd6e2cf1688-1 

00:13:33.682 --> 00:13:38.210
of the CT was most in keeping with an alternative to UIP pattern and
54ad07ad-5c5a-4b68-ba96-7bd6e2cf1688-2 

00:13:38.210 --> 00:13:43.394 
indeterminate for HP as there was no real convincing evidence of small airways
54ad07ad-5c5a-4b68-ba96-7bd6e2cf1688-3 

00:13:43.394 --> 00:13:43.919
disease.
5ce3490c-7c29-4d66-b7cc-8d22f96d8a84-0 

00:13:45.440 --> 00:13:46.840
She had serology done.
0e6c086a-e0f0-42a8-8fe1-7bae6c984a8d-0 

00:13:47.720 --> 00:13:52.600
This patient did undergo bronchoscopy and really had no significant lymphocytosis.
dabf94bd-da7a-4494-9c5d-6806a571101d-0 

00:13:58.540 --> 00:14:02.387
All right,
so this is the polling question #2 So
dabf94bd-da7a-4494-9c5d-6806a571101d-1 

00:14:02.387 --> 00:14:02.780
what?
8a3766c2-1819-41f4-affb-af7d4ea00190-0 

00:14:02.900 --> 00:14:03.740
What would you do?
16ed75fa-2e7b-42bd-ae3d-3f60b3538a7a-0 

00:14:03.740 --> 00:14:07.040
What would you say to the referring physician?
fa0d4806-368c-446a-a99f-0e3ca75e3a37-0 

00:14:07.040 --> 00:14:08.960
Yes, send them for surgical lung biopsy.
9951ece9-e276-4c36-8b68-b96fdd542358-0

00:14:08.960 --> 00:14:12.160
No,
don't send them for surgical lung biopsy.
4f36a4e9-5e3d-4c80-965b-5e992a585fc9-0

00:14:12.360 --> 00:14:15.080
Or lastly, send them for cryobiopsy.
05f438e4-1be9-4430-95f7-ab62dd8fc1d9-0 

00:14:15.080 --> 00:14:21.960
I think this one will be a little bit more mixed, so I'm excited.
e22df2fc-fda5-4e77-8e31-4f6cd82454de-0 

00:14:23.880 --> 00:14:28.560
We'll give everyone a minute or so for the results to come in.
4b734c3a-7776-4e91-b94b-35570b77aff3-0

00:14:33.990 --> 00:14:46.316
Get some more people voting all right see some more coming in your get your vote in
4b734c3a-7776-4e91-b94b-35570b77aff3-1

00:14:46.316 --> 00:14:57.909
even even if the options aren't great, we should all still get out and vote so
4b734c3a-7776-4e91-b94b-35570b77aff3-2

00:14:57.909 --> 00:15:05.099
come on OK,
I think we can we can close the poll
4b734c3a-7776-4e91-b94b-35570b77aff3-3

00:15:05.099 --> 00:15:05.979
there.
a6c886ff-4568-47b8-b5d2-d15b035fc2bb-0 

00:15:05.980 --> 00:15:08.500
We got a good number of responses.
8cb972d6-8e7e-4631-a968-34a3a08d53dc-0

00:15:12.380 --> 00:15:15.100
All right, so this is interesting.
c3c12b6c-9252-40b9-8a59-3c273cdbfdc2-0 

00:15:15.100 --> 00:15:21.776
So most people, so 62% said yes,
send for surgical lung biopsy, 14% no,
c3c12b6c-9252-40b9-8a59-3c273cdbfdc2-1 

00:15:21.776 --> 00:15:26.320
wouldn't do the lung biopsy, not worth the risk.
8348387b-2114-436f-9fb4-96eb8ef49c01-0

00:15:26.320 --> 00:15:30.240
And then 24% said send for send for cryobiopsy.
07a6afaf-084b-40fb-a39e-40d38276798f-0 

00:15:30.240 --> 00:15:39.020
All right, OK.
1892f197-2130-4263-84c5-0e66a4ef7c91-0

00:15:39.020 --> 00:15:43.380
So let's just loop back to our figures here just to remind ourselves when we
1892f197-2130-4263-84c5-0e66a4ef7c91-1

00:15:43.380 --> 00:15:47.740
when we might be thinking about doing something like cryobiopsy or surgical
1892f197-2130-4263-84c5-0e66a4ef7c91-2

00:15:47.740 --> 00:15:48.420
lung biopsy.
1983072b-396e-488d-933f-01719e9e9c4d-0

00:15:48.900 --> 00:15:54.881
So for when IPF is on the differential indeterminate for UIP or alternate
1983072b-396e-488d-933f-01719e9e9c4d-1

00:15:54.881 --> 00:16:00.540
diagnosis, which our patient fell into, discuss it in MDD if you can,
1983072b-396e-488d-933f-01719e9e9c4d-2

00:16:00.540 --> 00:16:02.480
then you think about it.
76bf0270-2e4b-4a0a-8033-72a9625c7493-0

00:16:02.480 --> 00:16:06.515
And then if we're thinking about it from an HP lens, you know,
76bf0270-2e4b-4a0a-8033-72a9625c7493-1

00:16:06.515 --> 00:16:09.525
we've gone through exposure, looked at the CT,
76bf0270-2e4b-4a0a-8033-72a9625c7493-2

00:16:09.525 --> 00:16:13.240
we've done a bronchoscopy with the BAL cellular analysis.
c773b914-9b97-4ca0-90e2-befa9cae6417-0 

00:16:13.560 --> 00:16:15.440
We've had an MDD discussion.
e40aba55-86d6-4965-a2ea-71e556bdb422-0 

00:16:15.600 --> 00:16:19.200We still haven't found a diagnosis and that's when we're thinking about it.
0de95d32-9132-4f21-9dac-ddc0abbf50cc-0 

00:16:20.320 --> 00:16:24.071
All right,
So ATS suggests we should be thinking
0de95d32-9132-4f21-9dac-ddc0abbf50cc-1 

00:16:24.071 --> 00:16:24.760
about it.
1d58db0e-1bb2-4c4f-9fc2-2b2f455d22d1-0 

00:16:25.840 --> 00:16:27.880
Why are we, you know, hesitant?
cea781df-e162-45a8-8198-1f3292ed4842-0 

00:16:28.480 --> 00:16:31.160
So really what is the risk of surgical lung biopsy?
90ccb91f-7702-4e99-89e8-9005e52d794a-0

00:16:31.760 --> 00:16:37.153
And I think this was a really important paper that was published in the US in
90ccb91f-7702-4e99-89e8-9005e52d794a-1

00:16:37.153 --> 00:16:39.920
2016 looking at inpatient hospital data.
43c4f9f5-6602-4fc6-837f-c8c0f19ff0f3-0 

00:16:40.840 --> 00:16:47.631
And so they looked at all patients who had a surgical lung biopsy for ILD using
43c4f9f5-6602-4fc6-837f-c8c0f19ff0f3-1 

00:16:47.631 --> 00:16:49.160
the hospital data.
284a0c62-df08-46b4-8dbe-5c2b8bfb97c3-0 

00:16:49.160 --> 00:16:54.720
So it wouldn't include any data after patients are discharged from hospitals.
94baa285-6b2b-48f0-949d-9539ff222223-0

00:16:54.720 --> 00:16:57.240
So this is just looking at their hospital stay.
f67704b6-4931-4680-84e9-471b1d7f7c28-0 

00:16:58.160 --> 00:17:03.573
And what they found was that the inpatient mortality after surgical lung
f67704b6-4931-4680-84e9-471b1d7f7c28-1 

00:17:03.573 --> 00:17:04.760
biopsy was 6.4%.
4b1dfc96-8db7-4e44-8272-1fe241db01cb-0 

00:17:05.120 --> 00:17:08.055
So, you know,
really quite high for a diagnostic
4b1dfc96-8db7-4e44-8272-1fe241db01cb-1

00:17:25.360 --> 00:17:29.107
So elective would be those patients who are coming from home, you know,
92863364-89b6-47bb-9045-e27cc3ad85c1-1

00:17:29.107 --> 00:17:32.073
for the lung biopsy,
whereas non elective would be those
92863364-89b6-47bb-9045-e27cc3ad85c1-2

00:17:32.073 --> 00:17:34.520
patients who are already admitted to hospital.
bdd53886-3391-4cb6-88d6-81a1530eebc4-0 

00:17:34.760 --> 00:17:38.675
You get consulted, you know,
as the respirologist who's on and you
bdd53886-3391-4cb6-88d6-81a1530eebc4-1 

00:17:38.675 --> 00:17:41.422
know, should we be sending this patient
bdd53886-3391-4cb6-88d6-81a1530eebc4-2 

00:17:41.422 --> 00:17:43.000
for a surgical lung biopsy
3c655c50-e234-4c51-949d-eed21a858021-0

00:17:43.000 --> 00:17:46.749
So that that would be the non elective and you know the difference is really
3c655c50-e234-4c51-949d-eed21a858021-1

00:17:50.400 --> 00:17:55.176
So in hospital mortality in the elective patients was 1.7%
3149999d-f721-4ec6-85d2-3d000920ff00-1

00:17:55.176 --> 00:18:01.293
versus about 16% in patients who underwent non elective surgical lung
3149999d-f721-4ec6-85d2-3d000920ff00-2

00:18:01.293 --> 00:18:01.880
biopsy.
d9eefbe8-1c35-46af-b4c2-89d0b868c55a-0 

00:18:01.880 --> 00:18:04.560
So very high in in non elective case.
34b86d2f-5a52-4c88-b77e-0449e9513d4d-0

00:18:05.080 --> 00:18:08.664
And they also looked at specific risk factors for mortality and they were,
34b86d2f-5a52-4c88-b77e-0449e9513d4d-1

00:18:08.664 --> 00:18:10.480
as you would expect, so comorbidities.
93da0975-0731-4563-9064-2b611ca73ed6-0

00:18:10.480 --> 00:18:13.752
So, you know,
five times higher odds of in hospital
93da0975-0731-4563-9064-2b611ca73ed6-1

00:18:13.752 --> 00:18:16.900
death if your Charleson score was more than two,
93da0975-0731-4563-9064-2b611ca73ed6-2

00:18:16.900 --> 00:18:19.040
your Charleston comorbidity score.
c8a5b306-dd7a-4d31-a796-f20abfad1d76-0 

00:18:19.440 --> 00:18:22.840
And then for age, so older age, which again is not surprising.
35967d4c-dad6-47fd-b7c3-78dc515b0eeb-0 

00:19:15.248 --> 00:19:18.774
being male,
older age and older comorbidities were
38b466be-2426-4ddf-b5a5-55921d470df3-2

00:19:18.774 --> 00:19:22.440
all associated with higher odds of death at 30 days.
bfa5338d-8c34-41fb-942c-6667a7e207e1-0 

00:19:23.440 --> 00:19:27.160
We also looked at center experience.
63808f22-33ff-4206-9d93-2d0f718b3c8e-0

00:19:27.360 --> 00:19:30.636
So we looked at the number of surgical lung,
63808f22-33ff-4206-9d93-2d0f718b3c8e-1

00:19:30.636 --> 00:19:36.243
number of surgical lung biopsies the center does in a year and we found that
63808f22-33ff-4206-9d93-2d0f718b3c8e-2

00:19:36.243 --> 00:19:41.849
centers who had higher surgical lung biopsy experience had improved survival
63808f22-33ff-4206-9d93-2d0f718b3c8e-3

00:19:41.849 --> 00:19:46.000
and it was particularly relevant for non elective cases.
6795caf4-74e8-4ba9-bce2-c666b65d6f69-0 

00:19:46.000 --> 00:19:48.737
And you know,
there's a lot of factors that go into
6795caf4-74e8-4ba9-bce2-c666b65d6f69-1 

00:19:48.737 --> 00:19:51.160
that volume outcome relationship and surgery.
2f2c2568-d12a-4116-a091-4051a692f77a-0

00:19:51.160 --> 00:19:53.897
So it's not, you know,
just about surgical expertise,
2f2c2568-d12a-4116-a091-4051a692f77a-1

00:19:57.345 --> 00:20:01.249
selecting the right patients to undergo the procedure and then also just the
2f2c2568-d12a-4116-a091-4051a692f77a-3

00:20:01.249 --> 00:20:02.720
experience of the whole team.
b3df0543-15d1-491c-a5b1-29315a9b7f75-0 

00:20:02.720 --> 00:20:06.650
So the anaesthetist and the, you know, pre and post surgical care that the
b3df0543-15d1-491c-a5b1-29315a9b7f75-1 

00:20:06.650 --> 00:20:07.960
patients receive as well.
5b06f6a6-24aa-4474-9ba9-4489914ccb89-0

00:20:13.800 --> 00:20:17.855
Summarizing all that data together just to highlight again the major risk factors
5b06f6a6-24aa-4474-9ba9-4489914ccb89-1

00:20:17.855 --> 00:20:19.400
for perioperative complications.
b6c46427-e8c5-44d7-a3c3-a01fea5b9634-0 

00:20:19.400 --> 00:20:23.354
So when patients have these,
we really are hesitant and essentially
b6c46427-e8c5-44d7-a3c3-a01fea5b9634-1 

00:20:23.354 --> 00:20:26.960
would not send them for a surgical lung biopsy at our center.
e3069d83-74dd-44a6-a00e-fd4b9c298dc6-0 

00:20:26.960 --> 00:20:31.632
So age over 75 years,
really significant comorbidities,
e3069d83-74dd-44a6-a00e-fd4b9c298dc6-1 

00:20:31.632 --> 00:20:32.800
lung function.
06ac99ed-38e8-4415-aae5-01e47f4e3a0f-0 

00:20:32.800 --> 00:20:38.001
So there's observational data that has shown that an FVC of less than 55% and a
06ac99ed-38e8-4415-aae5-01e47f4e3a0f-1 

00:20:59.760 --> 00:21:02.124
So you know,
patients who are already on Prednisone
418c0d3c-806e-4bd1-8c17-2d26c6c27f89-1

00:21:02.124 --> 00:21:04.579
are bone marrow,
we have a big bone marrow transplant
418c0d3c-806e-4bd1-8c17-2d26c6c27f89-2

00:21:04.579 --> 00:21:05.079
population.
ed357f38-b41c-48d9-b0eb-5f54cbfdc72b-0 

00:21:05.080 --> 00:21:08.836
We find that they do very poorly after lung biopsy and then certainly rapidly
ed357f38-b41c-48d9-b0eb-5f54cbfdc72b-1 

00:21:08.836 --> 00:21:09.800
progressive disease.
d8da4f1a-5864-45fe-b621-0571501167d0-0

00:21:21.680 --> 00:21:23.280
All right, so let's loop back.
594a1cd6-d97e-40ff-b8e6-eb3ee4ea5723-0 

00:21:23.480 --> 00:21:25.320
So when to consider a surgical lung biopsy?
ce1f12ed-8346-40ef-a1a0-89a236d36b73-0 

00:21:25.320 --> 00:21:26.680
So what do the guidelines say?
24fc93b1-9e4c-444b-9a9c-7f000d62f9cb-0 

00:21:27.360 --> 00:21:30.890
So for HP,
they say for patients with newly
24fc93b1-9e4c-444b-9a9c-7f000d62f9cb-1 

00:21:30.890 --> 00:21:35.464
identified ILD,
when the differential diagnosis includes
24fc93b1-9e4c-444b-9a9c-7f000d62f9cb-2 

00:21:35.464 --> 00:21:39.877
fibrotic HP,
the guideline committee suggests surgical
24fc93b1-9e4c-444b-9a9c-7f000d62f9cb-3 

00:21:39.877 --> 00:21:40.839
lung biopsy.
8129792f-4011-4183-8703-c19c2fb09b71-0

00:21:41.280 --> 00:21:46.864
When you've done all those other tests that we talked about, you know,
8129792f-4011-4183-8703-c19c2fb09b71-1

00:21:46.864 --> 00:21:52.842
extensive exposure evaluation post look
at the CT bronchoscopy with BAL and
8129792f-4011-4183-8703-c19c2fb09b71-2

00:21:52.842 --> 00:21:58.820
cellular analysis and and you really can't find a diagnosis then suggest so
8129792f-4011-4183-8703-c19c2fb09b71-3

00:21:58.820 --> 00:22:02.359
that's like the softer one not, not recommend.
0bae7c17-24f7-4094-b8a5-00e8c8cdbba2-0 

00:22:04.000 --> 00:22:10.517
And then for the IPF guidelines,
they suggest performing surgical lung
0bae7c17-24f7-4094-b8a5-00e8c8cdbba2-1 

00:22:10.517 --> 00:22:11.160
biopsy.
39d1b2fa-449c-421c-8f68-040c664ef2ff-0

00:22:11.160 --> 00:22:16.572
So this is the conditional recommendation if it's indeterminate for UIP or
39d1b2fa-449c-421c-8f68-040c664ef2ff-1 

00:22:16.572 --> 00:22:18.160
alternative diagnosis.
9e5120ae-e23c-45a9-bda8-71e8ed260e42-0 

00:22:18.480 --> 00:22:21.746
And then probably UIP gets an* which you know,
9e5120ae-e23c-45a9-bda8-71e8ed260e42-1 

00:22:21.746 --> 00:22:25.221
in subsequent sort of discussions and iterations,
9e5120ae-e23c-45a9-bda8-71e8ed260e42-2 

00:22:25.221 --> 00:22:30.643
I think everyone acknowledges that most patients with probably UIP would not,
9e5120ae-e23c-45a9-bda8-71e8ed260e42-3 

00:22:30.643 --> 00:22:32.520
should not go for a biopsy.
90ff7314-5bb5-4074-880f-32212d56a225-0

00:22:33.280 --> 00:22:39.631
And then a strong recommendation not to perform a biopsy when patients have a, 
90ff7314-5bb5-4074-880f-32212d56a225-1

00:22:39.631 --> 00:22:41.240
a UIP pattern on CT.
0debea11-ce57-49c1-84b7-66dce8ee85ca-0 

00:22:45.960 --> 00:22:47.840
OK, so how about what do I do?
da894d0e-18af-4598-ab80-43a4c75c67a8-0 

00:22:48.240 --> 00:22:49.280
A pragmatist.
8115f04d-1011-4405-963a-dca30fbc944d-0

00:22:50.960 --> 00:22:57.474
So I do consider lung biopsy for indeterminant or alternative UIP cases
8115f04d-1011-4405-963a-dca30fbc944d-1

00:22:57.474 --> 00:23:00.280
and or low confidence HP cases.
bde00cec-2b96-467e-abf5-06d0e29d12a2-0 

00:23:00.840 --> 00:23:04.820
I always discuss these cases in MDD - I realize that's not, you know,
bde00cec-2b96-467e-abf5-06d0e29d12a2-1 

00:23:04.820 --> 00:23:08.384
universally available,
but if you have access to an MDD and
bde00cec-2b96-467e-abf5-06d0e29d12a2-2 

00:23:08.384 --> 00:23:12.839
you're considering a lung biopsy,
I think those cases should be discussed.
daa8e224-8331-4f46-a738-bbc0e333e0d3-0 

00:23:13.680 --> 00:23:18.668
I think it's important really to consider the safety profile and center expertise
daa8e224-8331-4f46-a738-bbc0e333e0d3-1 

00:23:18.668 --> 00:23:21.710
and, you know,
really look at your patient safety
daa8e224-8331-4f46-a738-bbc0e333e0d3-2 

00:23:21.710 --> 00:23:25.299
profile, you know,
have a frank discussion with them about
daa8e224-8331-4f46-a738-bbc0e333e0d3-3 

00:23:25.299 --> 00:23:26.760
the risk versus benefit.
0ae4e607-b056-4305-b4c2-fa694a8fc14a-0 

00:23:26.760 --> 00:23:30.040
And I always ask myself,
is this result going to change management?
9da80830-fd85-4856-8bf9-844970907e01-0

00:23:30.800 --> 00:23:34.180
If no matter what the biopsy says, I'm just going to do the same thing
9da80830-fd85-4856-8bf9-844970907e01-1

00:23:34.180 --> 00:23:36.371
anyway,
then then I personally would not send
9da80830-fd85-4856-8bf9-844970907e01-2

00:23:36.371 --> 00:23:37.800
that person for a lung biopsy.
4df2ea37-d5b5-4537-b5f6-c3ebcff6fd68-0 

00:23:40.720 --> 00:23:42.520
OK, So then what about cryobiopsy?
cda31668-e96e-4c51-8a11-9b48a6d93186-0 

00:23:42.520 --> 00:23:46.560
So some of you suggested cryobiopsy for that that patient.
16a57adc-3b79-45c3-b1da-b300d9bbe825-0 

00:23:47.160 --> 00:23:51.537
So transbronchial lung cryobiopsy is a potential alternative to surgical lung
16a57adc-3b79-45c3-b1da-b300d9bbe825-1 

00:23:51.537 --> 00:23:51.920
biopsy.
d9446dc4-4325-4c62-a53b-ee28234af89c-0 

00:23:51.920 --> 00:23:56.920
So it's similar to transbronchial biopsy but employs a freezing probe and thus
d9446dc4-4325-4c62-a53b-ee28234af89c-1 

00:23:56.920 --> 00:24:00.920
obtains lung tissue samples that are larger and better quality.
67d0adc7-0e28-4d77-916e-873a6f786e09-0

00:24:01.240 --> 00:24:05.890
And so the overarching idea behind it is that it's less invasive,
67d0adc7-0e28-4d77-916e-873a6f786e09-1 

00:24:05.890 --> 00:24:11.246
potentially safer than surgical lung biopsy and can get you a larger tissue
67d0adc7-0e28-4d77-916e-873a6f786e09-2

00:24:11.246 --> 00:24:15.615
size that will be adequate for your pathologist to, you know,
67d0adc7-0e28-4d77-916e-873a6f786e09-3

00:24:15.615 --> 00:24:17.800
help with making the diagnosis.
df7a920b-73bd-43c6-aafd-c07047490fd5-0 

00:24:17.800 --> 00:24:23.051
And so if we think about transmolecular biopsy, so you know,
df7a920b-73bd-43c6-aafd-c07047490fd5-1 

00:24:23.051 --> 00:24:30.197
probably depends on how good you are or how, how aggressive you are, but you know,
df7a920b-73bd-43c6-aafd-c07047490fd5-2 

00:24:30.197 --> 00:24:34.760
you might get a sample that's 1mm to, you know, 2mm.
7bba609d-e57a-4f4e-8a91-3aa5d897cf64-0 

00:24:36.040 --> 00:24:38.907
And then with transbronchial and cryobiopsy,
7bba609d-e57a-4f4e-8a91-3aa5d897cf64-1 

00:24:38.907 --> 00:24:42.080
it depends on how long you deploy the freezing for.
744e05ed-2bce-4f7d-8d63-21b8b5074027-0

00:24:42.480 --> 00:24:45.404
And then the longer you deploy the freezing probe,
744e05ed-2bce-4f7d-8d63-21b8b5074027-1

00:24:45.404 --> 00:24:47.240
the higher the risk of bleeding.
6b796900-2fb2-46b4-ac6f-ff68290634e4-0

00:24:47.240 --> 00:24:51.120
So you know,
there's going to be variation there again,
6b796900-2fb2-46b4-ac6f-ff68290634e4-1

00:24:51.120 --> 00:24:55.000
but you know,
you're probably looking at something more
6b796900-2fb2-46b4-ac6f-ff68290634e4-2

00:24:55.000 --> 00:24:56.040
like 8mm to 12mm.
75e706c0-dbf5-4923-96aa-626a27effe38-0 

00:24:56.040 --> 00:25:00.941
And then obviously, you know, we get a nice large chunk from our
75e706c0-dbf5-4923-96aa-626a27effe38-1 

00:25:00.941 --> 00:25:07.350
surgical lung biopsy, which is, you know, going to be several centimeters, you know,
75e706c0-dbf5-4923-96aa-626a27effe38-2 

00:25:07.350 --> 00:25:09.160
more like 5 centimeters.
da1f9c94-2b64-4c45-af7f-c21259d9666d-0 

00:25:13.200 --> 00:25:15.440
All right,
And hopefully this video works for you.
95f7c5ee-fb1c-4d1f-8940-ae43120adcb9-0 

00:25:15.440 --> 00:25:18.350
But for those of you who haven't seen a crowd probe,
95f7c5ee-fb1c-4d1f-8940-ae43120adcb9-1 

00:25:18.350 --> 00:25:21.480
so this is a crowd probe here just showing the freezing.
915111cc-9b79-45ae-a15a-f7cd6cae1996-0 

00:25:21.480 --> 00:25:23.040
So basically you deploy the freezing.
550d13bf-6723-4215-aadc-54e16a8159db-0

00:25:23.040 --> 00:25:26.360
You can see that's like an ice bubble on the end.
845611c0-a91c-4185-b7d6-ddd4040f309c-0

00:25:26.840 --> 00:25:33.196
And so the idea is that you put it through, you do a regular bronchoscopy,
845611c0-a91c-4185-b7d6-ddd4040f309c-1

00:25:33.196 --> 00:25:37.348
you put it through the, the, the chamber in the, 
845611c0-a91c-4185-b7d6-ddd4040f309c-2

00:25:37.348 --> 00:25:41.586
the therapeutic chamber or the diagnostic, sorry,
845611c0-a91c-4185-b7d6-ddd4040f309c-3

00:25:41.586 --> 00:25:45.400
the therapeutic chamber in the bronchoscope.
e81cd4b3-dfae-40a5-942d-f2a20911e186-0 

00:25:46.120 --> 00:25:49.001
You deploy,
you go to wherever you want to take the
e81cd4b3-dfae-40a5-942d-f2a20911e186-1 

00:25:49.001 --> 00:25:51.716
biopsy,
you deploy the freezing and it freezes a
e81cd4b3-dfae-40a5-942d-f2a20911e186-2 

00:25:51.716 --> 00:25:52.880
chunk of lung tissue.
1b5debed-fabf-4b96-989d-8e23637b82ba-0 

00:25:52.880 --> 00:25:56.000
And then you pull the whole thing out the, the bronchoscope as well.
89d92817-169d-4beb-86cd-763a3cdfb8d5-0 

00:25:56.880 --> 00:26:00.080
And then you get a larger piece of lung tissue.
00a98f42-ad69-440e-80b3-f90fc2709618-0

00:26:00.720 --> 00:26:06.721
Shane likes to describe it as like the
image he has of Homer Simpson putting his
00a98f42-ad69-440e-80b3-f90fc2709618-1

00:26:06.721 --> 00:26:09.240
tongue on a frozen pole in winter.
d23c89f3-d0b8-45ad-b5f4-e18073bb2f1e-0 

00:26:09.600 --> 00:26:12.520
And then, you know,
a chunk of the tongue gets ripped off.
b01ca041-c3de-4b84-92e4-97a23c7e4efd-0 

00:26:12.560 --> 00:26:14.280
So it's also a good way to remember it. c8648c9f-bdbb-40fc-8f6c-9e5ce29a62dc-0 

00:26:16.440 --> 00:26:20.971
And so I say that the cold ice study was sort of really the big study with
c8648c9f-bdbb-40fc-8f6c-9e5ce29a62dc-1 

00:26:20.971 --> 00:26:25.503
transbronchial lung cryobiopsy where, you know, we thought, OK, you know,
c8648c9f-bdbb-40fc-8f6c-9e5ce29a62dc-2 

00:26:25.503 --> 00:26:27.800
maybe we can use this in our patients.
5d3a2f9f-dc24-4aa4-a7a1-e69d5bd24e38-0 

00:26:27.800 --> 00:26:31.860
And so this was a prospective study of 65 patients who underwent concurrent
5d3a2f9f-dc24-4aa4-a7a1-e69d5bd24e38-1 

00:26:31.860 --> 00:26:34.960
transbronchial lung cryobiopsy and surgical lung biopsy.
c70073bc-fcf6-44d4-9676-e5800ecd3ffc-0 

00:26:35.760 --> 00:26:39.858
And you know, in brief,
the results were that there was
c70073bc-fcf6-44d4-9676-e5800ecd3ffc-1 

00:26:39.858 --> 00:26:44.981
histopathologic agreement between transbronchial lung cryobiopsy and
c70073bc-fcf6-44d4-9676-e5800ecd3ffc-2 

00:26:44.981 --> 00:26:51.056
surgical lung biopsy 81% of the time and then there was diagnostic agreement after
c70073bc-fcf6-44d4-9676-e5800ecd3ffc-3 

00:26:51.056 --> 00:26:52.520
MDD 77% of the time.
12fa8cf3-95c5-4e49-8730-61b30a95631f-0

00:26:52.520 --> 00:26:55.040
So, you know, pretty reasonable results.
b4c686b8-9779-425d-b751-3f38023a1b96-0 

00:26:57.040 --> 00:27:01.680
The concordance with a surgical lung biopsy MDD was quite high.
5f8320dd-673f-4ac1-86bb-266989175c0a-0

00:27:01.680 --> 00:27:07.644
So 95% if there was a high confidence in
the diagnosis after transbronchial cryo
5f8320dd-673f-4ac1-86bb-266989175c0a-1

00:27:07.644 --> 00:27:08.160
biopsy.
245f09ba-c540-4a68-89ff-928ac063586b-0

00:27:09.760 --> 00:27:15.282
In those patients who had low confidence in diagnosis with the transbronchial lung
245f09ba-c540-4a68-89ff-928ac063586b-1

00:27:15.282 --> 00:27:20.005
cryobiopsy MDD about 1/4 change to an alternative diagnosis with high
245f09ba-c540-4a68-89ff-928ac063586b-2

00:27:20.005 --> 00:27:22.800
confidence after the surgical lung biopsy.
faee7e1f-cee9-4530-bef4-4e0e803db497-0 

00:27:24.240 --> 00:27:28.444
And so, you know,
really it seems like concordance was very
faee7e1f-cee9-4530-bef4-4e0e803db497-1 

00:27:28.444 --> 00:27:33.840
high if everyone felt good about the transbronchial lung cryobiopsy result.
3204f2cb-ed1d-4b8c-b335-75498b1fc938-0 

00:27:34.120 --> 00:27:38.111
However, if you know,
the there was low confidence in the
3204f2cb-ed1d-4b8c-b335-75498b1fc938-1 

00:27:38.111 --> 00:27:42.240
diagnosis, then, you know, the results weren't as striking.
e4add33b-7752-4afc-b56d-59ad708b80a1-0 

00:27:42.720 --> 00:27:46.225
There was in terms of complications, there was mild to moderate bleeding in
e4add33b-7752-4afc-b56d-59ad708b80a1-1 

00:27:46.225 --> 00:27:47.240
about 1/4 of patients.
bc9de60a-a145-44d5-842f-4390c638a541-0 

00:27:47.240 --> 00:27:49.960
That was really sort of the most significant complication. 
b37b8978-a74f-42dd-819b-75428e397786-0 

00:27:50.760 --> 00:27:54.914
And so, you know, as a result,
I would say transbronchial cryobiopsy
b37b8978-a74f-42dd-819b-75428e397786-1 

00:27:54.914 --> 00:27:57.080
is certainly emerging or has emerged.
ba4d6b00-baad-4f3a-a253-9a1adf10b88a-0 

00:27:57.080 --> 00:27:59.964
It's a possible alternative to surgical lung biopsy,
ba4d6b00-baad-4f3a-a253-9a1adf10b88a-1 

00:27:59.964 --> 00:28:03.720
but does require obviously the expertise and appropriate safeguards.
573c8043-3ad8-4616-a845-b34353d77047-0

00:28:03.720 --> 00:28:07.320
And so, you know,
won't be available in every center.
68495972-8252-4f9e-a068-a4731e914e75-0

00:28:07.960 --> 00:28:12.112
You know with the asterisks that you should be careful about those trans
68495972-8252-4f9e-a068-a4731e914e75-1

00:28:12.112 --> 00:28:16.550
bronchial lung cryobiopsy path
results with low confidence and you know,
68495972-8252-4f9e-a068-a4731e914e75-2

00:28:16.550 --> 00:28:18.200
it's certainly in our center.
0ad27336-0984-4c97-9f68-03455a05d7a6-0

00:28:18.200 --> 00:28:22.128
We do think that the distribution of disease may help with patient selection
0ad27336-0984-4c97-9f68-03455a05d7a6-1

00:28:22.128 --> 00:28:23.200
and diagnostic yield.
ead587dd-c3dc-4fcf-8a7a-2e8eadac152a-0 

00:28:23.200 --> 00:28:26.598
So, you know,
we are more likely to send patients who
ead587dd-c3dc-4fcf-8a7a-2e8eadac152a-1 

00:28:26.598 --> 00:28:29.871
have parabronchiovascular involvement, for example,
ead587dd-c3dc-4fcf-8a7a-2e8eadac152a-2 

00:28:29.871 --> 00:28:34.466
for cryobiopsy as opposed to where the disease is like really, you know,
ead587dd-c3dc-4fcf-8a7a-2e8eadac152a-3 

00:28:34.466 --> 00:28:36.040
peripheral and subplural.
f2ccf5b2-dcb7-4456-a7ad-ec2625cd7dcf-0 

00:28:44.000 --> 00:28:47.419
I thought I'd tell you about the cold study as well,
f2ccf5b2-dcb7-4456-a7ad-ec2625cd7dcf-1 

00:28:47.419 --> 00:28:52.000
which is a more recent publication from some people in the same group.
dff1d051-5a93-442f-bfd1-46a7be5e65f9-0 

00:28:52.000 --> 00:28:57.244
So this was a multi center RCT in the Netherlands and what they did is they
dff1d051-5a93-442f-bfd1-46a7be5e65f9-1 

00:28:57.244 --> 00:29:02.557
took 55 patients who after MDD where it was suggested they should have a lung
dff1d051-5a93-442f-bfd1-46a7be5e65f9-2 

00:29:02.557 --> 00:29:03.040
biopsy.
0f3b15d8-6535-4258-a666-2486818d64e3-0

00:29:03.520 --> 00:29:07.544
And they randomized them either to get immediate surgical lung biopsy versus
0f3b15d8-6535-4258-a666-2486818d64e3-1

00:29:07.544 --> 00:29:11.360
what they called the step up strategy where they did a cryobiopsy first.
fb51e9e1-92a6-4b9c-8a23-7e2466a404c8-0 

00:29:11.360 --> 00:29:14.936
And then if it was felt that the cryobiopsy wasn't enough to make a

fb51e9e1-92a6-4b9c-8a23-7e2466a404c8-1 

00:29:14.936 --> 00:29:17.671
diagnosis, 
they would send them for a surgical lung
fb51e9e1-92a6-4b9c-8a23-7e2466a404c8-2 

00:29:17.671 --> 00:29:18.040
biopsy.
b3fe2d8d-6466-47c3-8c86-d83118f0778c-0 

00:29:19.560 --> 00:29:23.235
And the primary endpoint for the study was a little bit different than what we
b3fe2d8d-6466-47c3-8c86-d83118f0778c-1 

00:29:23.235 --> 00:29:23.840
were used to.
5aff1a30-5147-4e6a-9f98-18ca9c3d4390-0

00:29:23.880 --> 00:29:25.560
So it was chest tube drainage.
41830423-f492-4c11-8a6c-1bd261395760-0

00:29:25.560 --> 00:29:31.440
So that was defined as any requirement for chest tube in the step up group.
d5f3a7bd-65b2-4bd7-8118-7d58f5f9bf80-0 

00:29:31.440 --> 00:29:35.383
So the group that went straight for cryo followed by surgical lung biopsy only if
d5f3a7bd-65b2-4bd7-8118-7d58f5f9bf80-1 

00:29:35.383 --> 00:29:35.720
needed.
05dd3eb1-37ab-470c-b069-843867eb93d2-0

00:29:36.560 --> 00:29:41.790
And then the primary endpoint was met if patients in the surgical lung biopsy
05dd3eb1-37ab-470c-b069-843867eb93d2-1

00:29:41.790 --> 00:29:45.680
group group required a chest tube for more than 24 hours.
fb5068eb-c47b-41d1-b1bd-cb4f0beaa85d-0 

00:29:45.680 --> 00:29:51.767
And they decided on this outcome like in consultation with their REB and with
fb5068eb-c47b-41d1-b1bd-cb4f0beaa85d-1 

00:29:51.767 --> 00:29:53.640
patient representatives.
b99a36e7-4615-4198-b0ba-2316dcdcafc5-0 

00:29:53.640 --> 00:29:57.040
So this was felt to be like an important outcome for patients.
238949e0-e64b-438e-bdbf-ac7af6ff4ff3-0 

00:29:57.600 --> 00:30:00.641
And then secondarily,
they looked at diagnostic yield,
238949e0-e64b-438e-bdbf-ac7af6ff4ff3-1 

00:30:00.641 --> 00:30:03.240
hospital stay, pain and serious adverse events.
07f80b1f-4efb-46e7-b6bf-fb9ff7465009-0 

00:30:04.200 --> 00:30:07.016
So you know,
in terms of their primary outcome,
07f80b1f-4efb-46e7-b6bf-fb9ff7465009-1 

00:30:07.016 --> 00:30:11.183
they did find that, you know,
not surprisingly it was less in the step
07f80b1f-4efb-46e7-b6bf-fb9ff7465009-2 

00:30:11.183 --> 00:30:14.000
up group versus the surgical lung biopsy group.
125fcb8f-50a6-4daa-afa5-9109a24be068-0 

00:30:14.000 --> 00:30:18.628
So almost half of patients in the
surgical lung biopsy group needed a chest
125fcb8f-50a6-4daa-afa5-9109a24be068-1 

00:30:18.628 --> 00:30:23.500
tube for more than 24 hours and versus 11% in the step up group in terms of you
125fcb8f-50a6-4daa-afa5-9109a24be068-2 

00:30:23.500 --> 00:30:27.520
know outcomes that you know we typically are quite interested in.
4f836172-e881-420d-b20e-04a3ed0801bf-0

00:30:27.520 --> 00:30:29.160
So diagnostic yield.
bc0f25ba-9757-4f64-b920-af52844d89f5-0 

00:30:29.160 --> 00:30:34.440
So in the step up group after the cryobiopsy alone it was 82%.
2edec1ee-5b98-41c0-9957-59d88cd30b48-0 

00:30:34.760 --> 00:30:39.734
It did increase to 89% when the subsequent surgical lung biopsy was
2edec1ee-5b98-41c0-9957-59d88cd30b48-1 

00:30:39.734 --> 00:30:45.293
performed after an inclusive trans bronchial cryobiopsy versus 88% for the
2edec1ee-5b98-41c0-9957-59d88cd30b48-2 

00:30:45.293 --> 00:30:47.999
immediate surgical lung biopsy group.
a43c015d-ae40-4383-a12a-41d934dc0226-0 

00:30:48.000 --> 00:30:51.750
So you know,
fairly similar and then hospital length
a43c015d-ae40-4383-a12a-41d934dc0226-1 

00:30:51.750 --> 00:30:57.695
this day was one day in the step up group versus 5 days in the surgical lung biopsy
a43c015d-ae40-4383-a12a-41d934dc0226-2 

00:30:57.695 --> 00:30:58.120
group.
1b7a5786-4343-433e-96c3-6d0f1923332a-0

00:30:58.680 --> 00:31:02.640
And then there was only one serious adverse event in the step up group versus
1b7a5786-4343-433e-96c3-6d0f1923332a-1

00:31:02.640 --> 00:31:05.280
12 in the the immediate surgical lung biopsy group.
9525db12-3de4-4a97-a6ed-66de06d6667e-0 

00:31:05.280 --> 00:31:10.840
So you know, small study,
but you know some more data.
1f30e0ab-b673-4336-a2de-01ef3dd5acf4-0 

00:31:13.720 --> 00:31:16.960
All right,
so when to consider cryobiopsy?
54f0c608-24dd-401e-a620-e03381bca9d8-0

00:31:16.960 --> 00:31:18.320
So what do the guidelines say?
7cc20c5d-b998-4183-a480-bd288514b2a5-0

00:31:18.760 --> 00:31:24.055
So the guidelines tell us if you have a patient with newly identified ILD and the
7cc20c5d-b998-4183-a480-bd288514b2a5-1

00:31:24.055 --> 00:31:26.962
differential diagnosis includes fibrotic HP,
7cc20c5d-b998-4183-a480-bd288514b2a5-2

00:31:26.962 --> 00:31:31.160
the guideline committee suggests transbronchial and cryobiopsy.
63fcf540-362e-4b74-811d-9bbdd7e2e9ba-0 

00:31:35.560 --> 00:31:39.543
In terms of IPF,
the most recent diagnostic guidelines
63fcf540-362e-4b74-811d-9bbdd7e2e9ba-1 

00:31:39.543 --> 00:31:45.192
basically suggest that trans bronchial lung cryobiopsy can be regarded as an
63fcf540-362e-4b74-811d-9bbdd7e2e9ba-2 

00:31:45.192 --> 00:31:50.769
acceptable alternative to surgical lung biopsy when you need histopathology,
63fcf540-362e-4b74-811d-9bbdd7e2e9ba-3 

00:31:50.769 --> 00:31:55.766
assuming that you have, you know, ascent access to a center with the
63fcf540-362e-4b74-811d-9bbdd7e2e9ba-4 

00:31:55.766 --> 00:31:57.360
appropriate expertise.
7a920202-5092-429b-96b9-d2fcd1e7fa87-0

00:31:57.720 --> 00:32:02.261
So there's a conditional recommendation, low quality evidence like a lot of our
7a920202-5092-429b-96b9-d2fcd1e7fa87-1

00:32:02.261 --> 00:32:03.000
stuff in ILD.
aae3a8ad-b141-4588-9f83-57562857037f-0 

00:32:03.120 --> 00:32:07.205
But basically the guideline said, yes, if you're thinking about surgical lung
aae3a8ad-b141-4588-9f83-57562857037f-1 

00:32:07.205 --> 00:32:09.719
biopsy,
you can also think about transbronchial
aae3a8ad-b141-4588-9f83-57562857037f-2 

00:32:09.719 --> 00:32:10.400
lung cryopsy.
75092b7f-5d25-433e-be63-524b6d4da1a8-0

00:32:12.680 --> 00:32:14.680
So what do I do?
627bb79e-9c9d-4100-8d59-212518291829-0

00:32:14.800 --> 00:32:16.360
Again, pragmatically?
aeefeb84-4377-4578-8dce-e1fde4926ffb-0 

00:32:16.360 --> 00:32:21.880
So I do consider cryobiopsy for cases if I am considering a surgical lung biopsy.
a6c92873-fbf3-4f1d-9172-f1eb23db1ddc-0 

00:32:21.880 --> 00:32:25.274
Again, you know,
we're fortunate to discuss these cases at
a6c92873-fbf3-4f1d-9172-f1eb23db1ddc-1 

00:32:25.274 --> 00:32:28.151
an MDD,
certainly important as always to consider
a6c92873-fbf3-4f1d-9172-f1eb23db1ddc-2 

00:32:28.151 --> 00:32:30.279
the safety profile, center expertise.
c1698b66-d89e-4530-9bdf-78ed1d68b12a-0 

00:32:30.280 --> 00:32:33.730
In terms of safety profile,
I would say that we are a bit more
c1698b66-d89e-4530-9bdf-78ed1d68b12a-1 

00:32:33.730 --> 00:32:38.056
aggressive with you know quote-on-quote sending sicker patients for cryobiopsy
c1698b66-d89e-4530-9bdf-78ed1d68b12a-2 

00:32:38.056 --> 00:32:39.480
then surgical lung biopsy.
4d1ed880-cecf-4f9b-865f-036e60279c8c-0 

00:32:39.480 --> 00:32:42.210
We feel that the safety profile is likely a bit,
4d1ed880-cecf-4f9b-865f-036e60279c8c-1 

00:32:42.210 --> 00:32:45.720
you know better for cryobiopsy then then surgical lung biopsy.
cdbd84e9-f234-40c7-9656-d21775276354-0 

00:32:46.120 --> 00:32:49.180
And then as I mentioned before, we do look at disease distribution,
cdbd84e9-f234-40c7-9656-d21775276354-1 

00:32:49.180 --> 00:32:50.440
some more central disease.
050426bd-33b1-4b51-bff6-45695deb7327-0

00:32:50.720 --> 00:32:54.008
I feel better about trying cryobiopsy and always I ask myself,050426bd-33b1-4b51-bff6-45695deb7327-1

00:32:54.008 --> 00:32:56.200
is this result going to change management?
8a7c4eed-5e40-42e2-8ad4-149ed4313438-0

00:32:56.200 --> 00:32:57.880
Because if it's not, then I don't bother.
8299f81b-9277-4feb-a589-3749662216b9-0

00:33:01.280 --> 00:33:04.771
All right,
so let's move on to some of the newish or
8299f81b-9277-4feb-a589-3749662216b9-1

00:33:04.771 --> 00:33:07.868
you know,
what I consider not widely available
8299f81b-9277-4feb-a589-3749662216b9-2

00:33:07.868 --> 00:33:09.120
diagnostic testing.
c2b0890a-c8b4-4554-bb74-93f95f8cb0e7-0 

00:33:09.120 --> 00:33:12.448
So briefly,
I wanted to mention the genomic
c2b0890a-c8b4-4554-bb74-93f95f8cb0e7-1 

00:33:12.448 --> 00:33:13.280
classifier.
bcceb2ff-cf74-42a3-818d-1e5657d51bb4-0 

00:33:13.280 --> 00:33:17.938
So we all know the addition of histopathologic data increases the
bcceb2ff-cf74-42a3-818d-1e5657d51bb4-1 

00:33:17.938 --> 00:33:21.680
confidence of our clinical radiologic ILD
diagnosis.
2bfe945e-2ec7-45cf-83d1-0aef7ce40090-0 

00:33:23.040 --> 00:33:26.129
Unfortunately,
many patients can't or won't undergo a
2bfe945e-2ec7-45cf-83d1-0aef7ce40090-1 

00:33:26.129 --> 00:33:29.962
surgical lung biopsy and we might be left with unclassifiable ILD,
2bfe945e-2ec7-45cf-83d1-0aef7ce40090-2 

00:33:29.962 --> 00:33:32.880
which is up to 25% of patients in certain cohorts.
e7ff125c-ee05-4552-ae11-5ad8d8ae7a79-0 

00:33:33.600 --> 00:33:38.682
And this Envisia genomic classifier was developed using machine learning and RNA
e7ff125c-ee05-4552-ae11-5ad8d8ae7a79-1 

00:33:38.682 --> 00:33:43.011
sequencing on surgical lung biopsy specimens to identify a molecular
e7ff125c-ee05-4552-ae11-5ad8d8ae7a79-2 

00:33:43.011 --> 00:33:45.960
signature that can predict UIP histopathology.
75e1654a-15da-497d-84cf-a9224bb26f92-0

00:33:45.960 --> 00:33:51.216
So they developed this molecular signature using AI essentially and then
75e1654a-15da-497d-84cf-a9224bb26f92-1

00:33:51.216 --> 00:33:56.688
subsequently tested and validated it on transbronchial biopsy specimens to
75e1654a-15da-497d-84cf-a9224bb26f92-2

00:33:56.688 --> 00:33:58.200
identify UIP pattern.
14ab9b5d-3d25-480a-b57d-6c9c41828c65-0

00:33:58.200 --> 00:34:01.560
It can also be done on cryobiopsy specimens too.
faa53930-d53e-4b44-a2c2-9894fafeae47-0 

00:34:03.480 --> 00:34:09.335
And so really what it does is it tells 
you it's a UIP pattern or a non UIP
faa53930-d53e-4b44-a2c2-9894fafeae47-1 

00:34:09.335 --> 00:34:09.960
pattern.
56735518-80e8-4c7f-b7d8-8db94b6a386d-0

00:34:10.040 --> 00:34:15.601
And you know, with this,
all this data showed it had a sensitivity
56735518-80e8-4c7f-b7d8-8db94b6a386d-1

00:34:15.601 --> 00:34:21.909
of 68% and a specificity of 92% for identifying the UIP pattern with
56735518-80e8-4c7f-b7d8-8db94b6a386d-2

00:34:21.909 --> 00:34:24.400
moderate diagnostic agreement.
0bc6a8c7-f1f3-4cd4-9d87-df0eda2a031f-0