108. Journal Club with BMJ Thorax – Bronchiectasis

We’re back with our 4th episode in our collaborative series with BMJ Thorax. This week’s episode covers four articles related to bronchiectasis and covers a range of topics in this domain including novel therapeutics, registry data to understand risk, and … Continue reading →

Episode Transcript

(00:16):
Everybody, welcome back to Palm Peeps. Thanks for
tuning in today. Make sure to like and
subscribe wherever you're listening to us and on
any of the social media platforms you follow
us on. Monty, it's been a little live
since we recorded. Always love to be here.
You're on service right now, so you're busy
bopping between things.
How are things going? Hey, Ferf. Yeah. It's
great. Great to be back with you, and

(00:36):
excited for another BMJ Thorax collaboration.
But, yeah, no. Service is great. Great time
of the year. Kind of still new
new fellows to the system. So it's always
great to work with new trainees at this
time of year, but excited to be back
with you all. We're thrilled to be bringing
back our fourth collaboration with BMJ Thorax today.
And, as we have talked about before on

(00:58):
prior episodes,
Thorax is one of the leading journals in
pulmonary and critical care medicine. And as always,
they continue to publish cutting edge science in
PCCM,
and we're excited to dive into one of
their most recent journal clubs today.
Yeah. This has been a great series. I
I think you guys have all enjoyed it.
It's been very popular. We've certainly enjoyed collaborating
with the folks at BMJ Thorax. And, we're

(01:20):
joined once more by doctor Christopher Turnbull. He's
the associate editor for education at Thorax.
He's a respiratory consultant and honorary researcher at
Oxford University Hospitals
with his work focusing on sleep related breathing
disorders. And Chris has really been sort of
our go to expert on,
understanding these articles, some of the implications, and
some of the research techniques. So, Chris, thank
you again for joining. It's always great to

(01:41):
have you back on Palm Peeps.
Thanks very much. Pleasure to be back with
you today. I'm really looking forward to getting
stuck into today's episode.
Wonderful, Chris. I know he's an honorary poem
peeper for sure.
We'd like to go ahead and meet the
author of the most recent journal club, who
is doctor George Jumont. George completed his medical
school at the American University of Beirut and

(02:02):
is now an internal medicine resident at UT
Southwestern
in his second year of training.
Prior to starting residency,
George was up in Boston and was doing
a research fellowship at MGH studying chronic lung
disease. George, so great to have you on
the show today. Welcome.
Thanks, Christina. Very happy to be here on
the show. I'm a big fan of the
podcast. I'm really happy to be here and

(02:22):
talk about this journal club. Great. And I
think a a topic that I'm particularly interested
in hearing more about is bronchiectasis,
and I feel like that's the common theme,
in the articles that you selected. And I
think this is really exciting. Right, there's some
new work in the field.
We're actually starting to see some novel therapies
emerge for the first time, and I think
it's important, right, to when we think about

(02:44):
bronchiectasis
as someone who does CF as myself, I
think of bronchiectasis in the setting of CF
a lot. But I think today we're gonna
talk about non CF bronchiectasis,
which is exciting.
But, George, before we get into some of
the specific article questions, I'd love if you
could just share with us, your overarching goal
in selecting these four articles.
Was there a common theme or educational value

(03:05):
you were hoping to highlight by doing so?
Yeah. For sure. So my goal was to
highlight both the exciting progress we're seeing in
bronchiectasis and at the same time the challenges
that remain. The field is gaining a lot
of traction as you just said, especially with
the recent FDA approval and the first targeted
therapy,
which we'll be discussing today.
To capture that momentum, I chose two randomized

(03:26):
trials and two large cohorts so we could
look at novel therapeutics at the same time,
look at some of the comorbidities and
other real world outcomes.
So my goal is to highlight the multidimensional
aspect and,
move toward precision medicine that the field is
witnessing at the moment.
That sounds great. I think that is a
really holistic way to sort of study this,

(03:48):
and I'm excited to dive in and understand
these trials a little bit better.
So let's talk about article one. So this
is bransokateb
in bronchiectasis,
the ASPEN trial.
Please don't correct me if I pronounce that
small molecule wrong, but I think that is
pretty close. Bronchiectasis
is something we all see in practice. I
think, in the non CF bronchiectasis

(04:08):
world, like, when I'm seeing patient in general
clinic, it can be a little bit of
frustrating because we're often talking about prevention,
area clearance, like, how to not make things
worse, but we've had very few targeted therapies.
So this journal club and this article seems
like a real time to delve into some
upcoming therapies that may be coming out. So
specifically for this trial, I think it's important

(04:29):
that we're highlighting for people that we're talking
about DPP one inhibition.
That's not something that I'm generally very familiar
with, but this is a mechanism of action
targeting neutrophilic inflammation. And that I am familiar
with it. We we've all sort of seen
that. If we've had to bronch these patients
or if they come in with infections, then
neutrophilic inflammation plays a central role in bronchiectasis
pathophysiology.

(04:50):
So, George, can you walk us a little
bit through the study design of this article?
Yes. Sure thing. So this was a phase
three randomized double blind trial that enrolled one
thousand seven hundred twenty one patients with non
cystic fibrosis bronchiectasis
across 35 countries, actually.
Participants were assigned to either once daily branzocatib

(05:11):
at ten milligram or higher dose of twenty
five milligram
or placebo,
and they were full for, fifty two weeks.
The primary end goal of this trial was
the, annualized rate of pulmonary exacerbations with secondary
outcomes like, time to first exacerbation,
lung function decline, quality of life, and the
safety of the new medication.

(05:32):
Awesome. Thanks so much, George, for kind of
setting the stage for this article. I think
one of the things that just struck me
was the sheer scale of trial, as you
said, with over 1,700 patients, which is, I
think, quite impressive in a disease like bronchiectasis.
But also, managing a trial across 35 countries
seems to be quite a huge undertaking.
And, Chris, I'm hoping that you can, comment

(05:53):
a little bit on, you know, what strategies
do you think the investigators used,
to account for the site to site variability
across the 35 countries?
And how much confidence should we have that
the findings are going to be generalizable?
Thanks, Christina. So I think the main way
that the authors in this study tried to

(06:13):
ensure that they balanced and,
adjusted for regional variability was by stratified randomization.
So in depending on which region
patients were recruited from, they stratified based on
on that region. So forty percent of the
participants were from Europe,
fifteen percent approximately from
The USA, and and then forty percent from

(06:35):
the rest of the world. And and they
stratified
into the placebo or,
men's socketive groups based on that factor.
That was also then included
in their modeling, so they adjusted for that
in their statistical models.
So I think that was pretty good in
terms of making sure that the results are
accounting for that geographic variability in the study.

(06:56):
I think in terms of the
confidence that we have in the findings of
this study, in terms of how generalizable it
is, I'd go back to the CONSORT diagram.
And and, actually, they they screened two thousand
two hundred and ninety six patients to recruit
just over their one thousand seven hundred patients.
That's about seventy five percent of the patients
they screened that they enrolled,

(07:17):
which I think is
suggests that this is pretty generalizable
and applicable to the patients that we're seeing
every day in our clinic.
Yeah. Thank you so much, Chris. That's great.
I love
best practices for reading a journal article and,
like, the CONSORT diagram as a place to
look for generalizability,
but also sources of bias is, I think,
one of the key practices. So if you're

(07:38):
listening to this and you're trying to read
studies and analyze on on your own, looking
at that is always a a huge help.
And I love this trial. I mean, as
Christina, as you said, we I feel like
we're cardiologists here. 1,700 patients, randomized control, placebo
control. Like, we're really gonna get some, good
information out of this. So, George, if you
could highlight for us what were the key
outcomes, and and how should we interpret them

(07:59):
in the context of prior evidence?
The trial met its primary endpoint with both
the higher dose and the lower dose reducing
exacerbation rates compared to placebo.
Patients on bransocatib
averaged about one exacerbation per year versus 1.3
in the placebo group corresponding to a rate
ratio around 0.8.

(08:21):
Time to first exacerbation was also delayed, and
nearly half of patients on treatment remained exacerbation
free at the one year mark compared to
forty percent of the, patients in the placebo
arm.
Additionally, quality of life improved,
and the higher
the dose of presocatib
showed smaller FEV one decline, twenty four milliliter

(08:43):
versus sixty two milliliters with placebo.
So putting all of this together, it builds
on the prior phase two data and positions
presocatib as the first therapy with consistent evidence
of benefit in bronchiectasis.
Great. Thank you for walking us through that.
You know, as you mentioned, the exacerbation reduction
is

(09:03):
clinically meaningful, statistically meaningful.
You also mentioned this lung function decline, and
I find these are always tough. Right? So
you're talking about, a decline of 22 milliliters
versus a decline of 64 milliliters. When you
think about that, how clinically significant is a
difference like that in in PFT function?
Yeah. I agree. That absolute difference in FEV
one decline was around 40 milliliters over a

(09:26):
year, which is modest and probably not something
patients would notice in isolation.
However, looking at it, it's consistent with the
overall signal benefit.
If you combine it with the fewer exacerbations
per year, the better quality of life, it
adds to the case that ransukative
is, modifying disease in a meaningful way, but
I wouldn't think about it in isolation and

(09:48):
especially would not discuss it with patient in
isolation.
Yeah. And it'll be interesting to see more
long term follow-up because if it extends and
it's 400 milliliters over ten years, that might
be more meaningful at what or if it's
fixed, after the the one year. So be
interested to see what their phase four and
registry studies look like.

(10:09):
Yeah. And I love that love that your
aspect, George, too. Right? Just not taking it
into isolation.
How do you put all of this in
context when you're talking about patients who, you
know,
those with bronchiectasis
are going to clinics. They're probably hearing about
this and gonna wanna be talking to their
provider. So how do we kind of put
this into the context? And I I really
liked how you explained putting everything together.

(10:31):
And to go ahead and close our discussion
on this first journal article, Chris, I have
one more question for you. What gaps and
evidence do you still think need to be
filled before Ren Sokatib could realistically, you know,
actually become part of guideline based care moving
forward?
Yeah. Good question. I think we've touched on
this a little bit, already in in,

(10:51):
Dave's previous comments, really. I think that long
term efficacy data will be important to see
and looking perhaps at some of the other
associated outcomes that we know are important in
non CF bronchiectasis
like cardiovascular
outcomes, for example.
I think another area and gap that probably
is worth highlighting was that whilst this study

(11:12):
enrolled
adolescent participants,
their confidence interval for that group was very
broad because they had very few participants in
that group. So I think that's an area
I'd like to see more data on is
really how how
effective is this in adolescents.
Perhaps
also things like in patients with
the subgroups of having COPD or asthma,

(11:34):
it would also be helpful to know
whether this is more effective or whether they
should have a biologic and look perhaps for
some comparative data as what should we be
choosing for those exacerbating patients in with other
airways disease.
Great, Chris. Yes. I love that. So many,
additional opportunities to study this and yes. But,
really, I think exciting talking to,

(11:55):
those faculty members here who do bronchiectasis. I
know they're very excited about the study and
the, you know, potential implications it has. So,
we'll hear more in a potentially a future
journal club,
on more more studies that get done.
But we're gonna go ahead and turn our
attention to article two,
George, which you selected as the AIRLEAF trial,
a phase two multicenter,

(12:17):
randomized, double blind, placebo controlled study looking at
a reversible
kathepesin c inhibitor to determine its efficacy in
reducing exacerbation risk among adults with bronchiectasis.
George, instead of, you know, trying to pick
two different articles where Dave and I can't
necessarily say the names of the medications,
What drew you to highlight the paper for
Journal Club, and how should we see this,

(12:38):
in the context
of bransokatib, which we just talked about and
other evolving treatments in non CF bronchiectasis?
Yes. So I wanted to highlight this trial,
especially after the, bransukatib trial to show that
the the pipeline for bronchiectasis is no longer
limited to no agents or a single agent.
Bransukatib has been or has already made it

(12:59):
to phase three and received FDA approval,
but get the absence c inhibition
represents a complementary approach to the same pathway
of neutrophil inflammation that they was talking about
earlier.
Even though AirLeap was smaller and a phase
two trial, but, as you mentioned, Christina, it
was rigorously designed,
And it signals that multiple therapeutic strategies are

(13:19):
moving forward, which is exciting for a disease
that historically hasn't had any approved targeted treatments.
That's great. Yeah. I love that we're talking
about multiple targets. And if you can't
say, you can just say BI1291583.
That rolls off the tongue very easily.
One thing that's interesting about this, and especially
in the article analysis standpoint, is that it's

(13:41):
a phase two. Now phase twos are super
important. Phase one as well. We're often used
to reading the phase three trials that show
up in sort of our largest journals.
But, reading a phase two and understanding
it is a little bit different. And so,
for example, in this one, they use this
model dose response analysis. So in a phase
three, you might have two doses of a
drug and look at the efficacy. This is

(14:01):
sort of a a broader one. And so,
Chris, I was hoping you could walk us
through what this means, a model dose response
analysis, and how we should think about it.
Yeah. So this is a really interesting design,
in terms of how they looked at, the
study. And I think you you've highlighted the
key reason as to why they did this,
in in my opinion, was because this was
a phase two study, so including multiple dosing

(14:23):
regimens,
rather than a phase three where you might
have that data and selected the best dose
to take forwards,
although not necessarily as as we saw in
the Bren Sockative study. So what this modeling
enabled them to do was to look and
assess different
dose relationships
between,
the drug and dose response relationships between the

(14:45):
drug and the outcome,
modeling as to whether those relationships were either
linear or nonlinear
and assess those in their statistical model
across those different doses in the same model.
And that enables you to increase your statistical
power and to look at an outcome point.
I think the

(15:06):
you know, this
is helpful for phase two studies where you
got those multiple doses and allows you to
then look at an outcome there, but I
think it probably wouldn't be the the the
design that you would take forwards in more
definitive studies in the future.
Thanks so much, Chris. I always enjoy these
collaborations because we get to learn about, you
know, four amazing articles, but I also like

(15:27):
how you get you get to highlight different
methods and data analysis that are used, which
is I find, you know, particularly important as
I'm hearing about this. So thanks for sharing
that.
George, wanna go back to you now and
just you know, I'm hoping that you can
tell us, this, as you said, was a
regularly designed study, exciting, potentially new therapeutic.
What were the primary and secondary outcomes of

(15:48):
the study, and what do you think was
the most clinically important takeaway that you wanna
share with listeners today?
Alright. So the trial randomized three hundred twenty
two patients across four arms, three different doses
of BI one two nine one
five eight three, and a placebo
for up to forty eight weeks. So the
primary endpoint was time to first exacerbation.

(16:10):
And using the, model dose response analysis that
Chris was talking about, they found a significant
dose response relationship overall.
However, individually, the two point five milligram and
the five milligram groups, which are the lower
doses,
showed a trend towards fewer exacerbations, but the
results were not did not reach statistical significance
compared to placebo.

(16:32):
Safety looked reassuring overall with skin related events,
being the most common at higher doses.
So back to your question, Christina, I think
the main clinical takeaway is that this drug
class is promising. However, we still need
larger confirmatory trials before we move towards
implementing this in guidelines

(16:53):
or, talking about this with patients at all.
Agree, George. Thanks so much, for saying that.
I think it's kind of right this this
trending towards significance, which I think is important.
You just alluded to this, but I know
this is kind of a common question or
we get we're reading an article where it's
not statistically significant, but looks promising, as I
said, trending towards significance.

(17:13):
Would you feel comfortable at this time, you
know, discussing this class of drugs with with
patients that you may be seeing, or do
you think it's still too early? I I
may be able to gauge your gauge your
answer because of your last comment, but wanted
to see if you could just, comment on,
you know, how would you how would you
respond if a patient asks you about this,
if you're seeing them in clinic or in
the hospital?

(17:34):
Yeah. I'd say it's definitely too early to
bring it up into routine clinical conversation
outside of trials.
I think right now, bransoketev is the agent
with the strongest evidence and the NFDA approval,
while cathepsin c inhibition is, still very much
in the early investigational stages.
But it's reassuring to patients to know that
beyond Bransukative, there's a growing pipeline of therapies

(17:56):
being studied
that may, soon expand our options. But at
the moment, we're still limited with whatever,
is is more advanced and ready for,
prime time versus
the therapeutics that are still in trial phases.
Yeah. It makes sense to me for sure.
As as Christina alluded to, I think our
dual purpose in this series is to both

(18:17):
highlight really interesting articles that are promising or
or practice changing in pulmonary and critical care
medicine, but also to make people better
at reading journal articles and then maybe better
at conducting their own research, because we know
that's an interest of our listeners.
So to that end, Chris, I was gonna
ask you, this is a phase two as
we've highlighted.
So maybe not ready for prime time as

(18:38):
George just said. You know, just giving us
some information to go on. So what was
the the next follow-up trial design that would
help us get to that more definitive answer
of this is a a truly therapeutic and
safe, clinical option for our patients.
Thanks. So I think the next step for
this agent, as we've all alluded to, is
is a similar study to the branzocatib,

(19:00):
study that we looked at first. So a
phase three multicenter
randomized control trial,
potentially just taking forwards the single dose which
was most effective from this phase three and
and doing that one to one against placebo.
They may potentially want to take forwards two
of these doses and do one to one
to one randomization.
The data that they've gotten from this study

(19:21):
will be very helpful
in informing the power calculation so that they
get the appropriate sample size for that phase
three study.
And I think that's absolutely what we need
before we can definitively say whether this is
gonna be an option for our patients.
Yeah. Absolutely. So we'll be on the lookout
for that one. You guys have to come
back for another journal club in probably a

(19:43):
few
years. We'll look at that study.
Alright. Well, let's turn to the third study
highlighted, George. Now this is a article with
about five year outcomes in bronchiectasis
and nontuberculous
mycobacterial
infection.
The first two, as you said, were randomized
controlled trials at different phases that we've discussed.
But I was hoping you can tell us
about the study design and, cohort analysis utilized

(20:06):
for this study.
Yeah. So moving away from trials,
this is a longitudinal analysis from the US
bronchiectasis and NTM research registry.
This registry includes over
two thousand six hundred patients with CT confirmed
bronchiectasis.
About fifty nine percent of these patients had
NTM identified at baseline, and they were followed

(20:28):
up for five years to look at outcomes
like mortality,
lung function decline, exacerbations, and hospitalizations.
Thanks, George. And, again, yeah, different cohort that
was used. I mean, I feel like, looking
at CF, I've been able to benefit from
using our national registry data,
which has some positives as well as negatives,

(20:48):
but obviously, still great to do and produce
some fantastic research. But, Chris, I'm hoping you
can share a little bit. When we're thinking
about large registry,
cohorts, what are some strengths and pitfalls that
you see regarding using these registry data for
longitudinal outcomes?
I mean, I think the
registry data can be extremely helpful, can't it,

(21:10):
in terms of helping us understand
aspects of our care.
One of the real strengths of registry data
is it's a potential way of leveraging very
large sample sizes, so collecting large amounts of
data from patients across
different settings in in a country across across
multiple countries.
That data is real world as well, rather

(21:32):
than necessarily
having inclusion exclusion criteria that you get in
randomized control trials, which can mean that you
cut down and make a less generalizable
population.
There's the potential, as they have done in
this study, to follow people up over a
long long term basis, so to provide that
real longitudinal
data, which,
is incredibly helpful.

(21:53):
I think then the pitfalls in,
registries really come around how you set it
up and then the quality of the data
that you get going into that registry. So
are you relying on
information from patient notes and retrospective
data, or are you able to collect large
amounts of prospective data with good data quality,

(22:15):
for all of your outcomes?
I think another potential pitfall which registries can
fall into is it's often difficult to determine
whether
the results
represent cause or effect,
and and that, when you're certainly looking at
interventions,
can be influenced by patient choice or clinician

(22:35):
behavior.
And I think that's where we need our
randomized control trials still to really tell us
if an intervention is working.
And I guess you're you're finally,
I've spoken about them being real worlds and
generalizable,
but that really depends on how good you
are at getting a representative sample that you're
collecting
across your patients. So how easy you make

(22:56):
it to put people into the registry,
how much resource you have to do that
to enable you to have that generalizable
real world data.
So true, Chris. Thank you for commenting on
all of those. And I think as you
as you mentioned, George, this purpose of this
study was to look at five year outcomes
in patients with bronchiectasis.
So I'm hoping that you can walk us

(23:17):
through the key results of this study.
Yes. So the primary outcome was the five
year mortality, which was about twelve percent.
And interestingly, there was no significant differences between
patients with and without NTM
when comparing this five year mortality.
The predictors of mortality were more traditional,
things like lower baseline FEV one, older age,

(23:39):
male sex, and prior hospitalizations.
Lung function decline was similar across the groups
as well with roughly 38 milliliters
per year. And while exacerbations, the hospitalization rates
were stable overall.
Patients with baseline NTM actually had fewer exacerbations
compared to those without,
which, is surprising.

(23:59):
When you look at the literature, this is
not usually the trend things are, but this
study
found that they had fewer exacerbations.
Joy, any thoughts about that?
Any thoughts about explanation of why that would
be or any thoughts that the authors could
sort of share?
One explanation is that

(24:20):
since it's,
registry,
data, I think that
they did not
differentiate between NTM
colonization versus
active NTM disease, which can bias
some of these findings.
The other thing,
which was highlighted in the article was that
maybe the actual diagnosis can trigger referral to

(24:42):
specialized centers and so patients can get
more holistic care or more more specialized care
compared to, for example, a patient who does
not have any NTM in their sputum or
in their cultures.
So
these are some of the explanations to these
findings, in my opinion, the author's opinions.
Yeah. Yeah. That's really interesting. Thinking about the

(25:04):
referral and how you end up getting into
the registry is a really interesting way and
and sort of highlight some of the weaknesses
and strengths,
potentially that Chris was talking about. Yeah. And
you mentioned this NTM colonization from active disease.
Such an interesting question in this cohort. Right?
Because NTM is a risk factor for bronchitis.
Bronchitis is a risk factor for NTM. You
know, there's been a lot of debate about

(25:24):
NTM treatment. Chris, just curious if this adds
any
nuance or or other thoughts about how we
think about that or apply these findings based
on some of these limitations.
Yeah. I mean, I think it
I think it's difficult to really interpret this
result, isn't it? I think it's a challenging
finding,
and and it challenges conventional wisdom.

(25:44):
But I think,
really, what you would want to know is
what we've all been just speaking about is
knowing that granularity
of whether this really is this just a
single isolate of,
a particular type of NTM which is likely
to be commensal rather than pathogenic?
Or or is this truly
NTM disease, and NTM disease is some in

(26:05):
some way protective here?
I'm not sure that is the case, and
I think
it's more is needed to understand what this
result truly means. But it's interesting in that
it it goes against what we've perhaps all
been taught.
Yeah. Very more to come, but an interesting
sort of hypothesis generated and finding for sure.
Yeah. I know. We'd be interested to see

(26:26):
because I think a lot of people will
probably have questions, right, of, like, how do
we explain this to to patients? How do
we explain this kind of in the in
the bronchiectasis
community? But I think, Mennel, this is kind
of a great study,
as we talked about, you know, pros and
cons of using registry data. But I think
overall, it was interesting study and glad that
you selected this one, George, for us to
talk about.

(26:46):
But we'll go ahead and turn to our
final journal article of the day, which is
focused on the prevalence and impact of anxiety
and depression
in patients with bronchiectasis
using the bronch UK national cohort.
George, why did you feel this study was
important to feature? And I guess my my
follow-up question to you on that as well
right now is, how do you think these
findings might influence clinical practice or future research

(27:08):
in bronchiectasis?
Yeah. Thank you for that question. So I
I wanted to include this study because it
reminds us that bronchiectasis,
like other chronic respiratory diseases, are not just
about infection, inflammation, and lung function.
Anxiety and depression are very common, and they're
underrecognized,
and they have real word impact on the
outcomes of bronchiectasis.

(27:30):
Bringing mental health into the conversation can shift
us to a more holistic model of bronchiectasis
care. And we can actually start doing that
by
screening,
utilizing some of the short and quick questionnaires
that we have,
at our disposal in clinics like the PHQ
and the GACC questionnaires so we can
identify,

(27:50):
anxiety and depression early on and,
having pathways for referral to psychology, psychiatry,
or any other needs that are readily available
for, clinicians in in clinic to offer the
best care possible
and help patients feel that their care is
more person centered versus just focusing on the
lungs.
Yeah. 100%. I feel like this is one

(28:10):
of those interesting,
and very important topics. And when we're counseling
patients, I feel like there's a lot of
therapies that we can say will increase your
six minute walk by this amount, but then,
you know, the patient centered, how are you
gonna feel about this? How is your symptoms
gonna be? What's your quality of life?
It's something that's always a secondary, and we
might not talk about as much. So I'm
really glad you're highlighting this.

(28:32):
You mentioned this is another cohort study. We're
using a a national cohort for this. Cohort
studies can be conducted and studied a little
bit differently.
Just hoping you could walk us through the
study design of this. And was this just
descriptive? Were they looking trying to look at
any timing of exposures?
How did they go about trying to describe
this a bit further?
So, yeah, this cohort study actually had, one

(28:55):
thousand three hundred forty adults with CT confirmed
bronchiectasis.
It's the Bronch UK national cohort.
Anxiety and depression symptoms were measured using the,
well validated hospital anxiety and depression scales.
And, the authors also looked at the outcomes
including disease severity, quality of life, and out
and exacerbation optimizations.

(29:15):
As you said, it's more descriptive
versus the, previous study, which looked at five
years outcomes.
This is more,
focused on the anxiety and depression
outcomes now.
That's great, Georgi. And I'm hoping, yeah, if
you wouldn't mind just extending a bit. Yeah.
What were the rates of anxiety and depression,
and how did they affect outcomes in this
study? Yeah. So the,

(29:37):
actually, the the authors found that one in
three patients had clinically relevant anxiety and one
in five had depression.
These rates were well above the general population.
And one notable feature in this paper was
the substantial proportion of these patients who did
not have any mental health diagnosis prior to
enrolling, which was twenty six percent for the
anxiety group and sixteen percent for depression.

(30:00):
This highlights the under recognition in routine care,
especially when, as Dave was saying, we were
focusing more on the six minute walk,
the,
FEV one, and, some of these comorbidities go
unnoticed.
So patients with anxiety and depression also had
worse quality of life scores. They had more
severe disease
and more frequent exacerbations.

(30:21):
For example, patient with depression had a one
point eight fold higher risk of hospitalization,
and their first time to severe exacerbation was
also shorter compared to patients without depression.
This highlights the clinical impact of mental health
as we were talking about in the holistic
care bronchiectasis.
Yeah. Definitely not something for us to
to forget about or take lightly at all.

(30:43):
And anxiety and depression is associated
with lung diseases is not uncommon at all,
certainly not isolated to bronchiectasis.
So, Chris, curious if you've seen,
other interventions,
in bronchiectasis or other respiratory diseases
that have been successful or things that you
think would be worth studying based on a
result like this?

(31:05):
Yeah. I think it's a really interesting result,
isn't it? I I guess one thing to
say before coming on to that is,
again, with the cohort studies, one of the
challenges is that you're seeing anxiety and depression,
which is linked to that increase in rates
of hospital admissions, etcetera.
Now it's always hard to to tease out
cause and effects in a cohort study and
and you could argue it the other way

(31:25):
around that those people who are have more
severe disease and more likely to be admitted
to hospital are more likely to have anxiety
and depression associated with that. It's very difficult
to tease that apart. Nevertheless,
I think that does not detract from the
important message that this is an incredibly important
topic for us to tackle and and how
we do that I think is a challenging

(31:46):
question
because of the the size of the scale
of the problem finding in this study approximately
a third of individuals who have,
mental health,
issues which are undiagnosed.
So I think
my approach and what I'd like to see
taken forwards would be whether there are things
that can be done in the structured consultation

(32:06):
within the bronchiectasis
clinic
that can help and improve this impact. So
are there,
educational packages and training that can be delivered
to staff who are already seeing these patients
rather than us needing to refer all patients
to psychiatry or psychologists for support.
I think that wouldn't be a sustainable model
certainly within the NHS in in The UK.

(32:29):
So that will be my my goal would
be, look, Are there things that we can
do about education and talking to patients,
perhaps cognitive behavioral therapy based approaches
that can help and and and support this
anxiety?
Of course, if you're doing that, you need
to make sure that you are picking up
those individuals who do need psychiatric and psychological
support well,

(32:51):
because some of them certainly will do. But
I think that if you were to refer
simply refer everyone to psychology or psychiatry or
to prescribe
an antidepressant medication for these, I think that
will be the wrong approach.
Yeah. Absolutely. Yeah. We should we should get
some shirts made up that are, say, Paul
and Phips BMJ Thorax Association is not causation.
Right? And then we can always take our

(33:12):
lessons, but we can still
certainly let it influence our practice.
And to that, we'll come to our final
question of the day. So, George, you know,
you're you're training. You're in residency. You're in
training. You've done a lot of research on,
respiratory diseases.
How does a study like this and that
association
practically influence you if you were in clinic
and you were seeing a patient with bronchiectasis?

(33:34):
How do you think it practically should, influence
the bronchiectasis
care for these patients?
Yeah. I think it, as Chris was saying,
knowing about these comorbidities,
knowing how,
common they are, I think I would start
screening more whether in clinic, whether,
trying to implement some multidisciplinary
approaches

(33:55):
during the various care of patients,
hospitalized patients, outpatient pay
clinic visits.
I think I would start screening my patients
more, and I would talk about I would
have these conversations with them just to create
a safe space to share,
and to make sure that they realize that
even though it's a lung predominant disease, it
has effects on other

(34:17):
functions. And it has multiple comorbidities that we're
not very
familiar with and we don't talk often about.
I love that, George. Thank you for for
sharing that. And, yeah, right with these chronic
lung conditions, as you said, mental health is
definitely important.
And, you know, you you nicely noted, you
know, how can we expand from a multidisciplinary
approach? And I know sometimes social workers, mental

(34:37):
health coordinators,
are parts of chronic lung disease teams. And
I think one thing I'm doing in in
clinic when I see CF patients too, because
this is also prevalent in that population,
and when I get to work with trainees,
you know, I was like, yes. My my
initial questions may be focusing on lung, lung
symptoms, looking at lung function. I'll do extrapulmonary
manifestations, but I told them I always end
the day looking, at mental health and making

(35:00):
sure that that gets incorporated into my day
to day practice. And to Chris, to your
point, though, right, we can if we recognize
that there may be
additional assistance or if there's concern for for
mental health, how to make sure that we
are able to refer in those settings. So
we can identify a problem, but we need
to be able to have a a plan
going forward if we do feel that, someone

(35:20):
needs any type of follow-up. So I I
love that kind of just practical approach that
we can start doing, ourselves and then working
with our multidisciplinary
teams.
But, Georgie, pick four fantastic articles, I think
really impactful,
you know, from our initial one, cutting edge
anti inflammatory
drugs,
to registries reframing outcomes, and the overlooked burden
of mental health.

(35:42):
So thank you so much for the work,
George, that you did on this. And, Chris,
as always, I know Dave and I really
look forward to these collaborations
and would just love if you wouldn't mind
reminding listeners on how they may be able
to work with you on a future journal
club going forward.
Thanks. Yeah.
So the the main focus of journal club,
in within BMJ Thorax is to highlight

(36:02):
four research articles from roughly the last twelve
months, some high impact journals, just as George
has done today.
And,
they tend to focus on one topic. So
today, bronchiectasis,
it could be a different area like sleep
medicine, asthma, COPD, lung cancer, etcetera. And if
people are interested in contributing to that, they

(36:23):
can,
send me an email.
My email address is [e-mail],
and I'm sure we can put a link
to that. So please do get in touch
if you're interested in taking part, and, I'll
tell you more details.
Definitely. Highly encourage it. If you need some,
suggestions or coming up, definitely reach out to
Monty and I. We're happy to to help

(36:44):
and direct you over to Chris.
Thank you, George and Chris, for coming on
and for your time, and and thank you
all for listening. This episode was written, produced,
edited by myself and Christina Montemayor,
music's original music by Eric Rogers, and we'll
see you next time.