April 16, 2025 • 45 mins
On this episode, recorded in front of a live audience, Cardiologist Dr. Michael Koren is joined by pulmonologist Dr. Mitchell Rothstein to discuss Chronic Obstructive Pulmonary Disease (COPD). COPD is obstruction of the lungs, making it hard to breathe and represents a significant health challenge . It affects millions of Americans and is a leading cause of mortality, yet receives disproportionately low research funding compared to conditions with fewer annual deaths. The doctors explore this chronic lung condition from its biological mechanisms to the latest treatment approaches, highlighting the critical need for increased awareness and research investment.
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Episode Transcript
Available transcripts are automatically generated. Complete accuracy is not guaranteed.
Announcer (00:00):
Welcome to the MedEvidence! podcast.
This episode is a rebroadcastfrom a live MedEvidence!
presentation.
Dr. Michael Koren (00:06):
I'm really excited to learn about COPD
chronic obstructive pulmonarydisease and you've been spending
your whole career as an experton this and I don't know anybody
more knowledgeable, so let'srun through it.
Let's educate everybody aboutCOPD.
Dr. Mitchell Rothstein (00:22):
And just before I get started, Dr Koren
was very concerned that I hadtoo many slides and I was going
to take too long.
So he took up the first fiveminutes of my time and I said,
well, I'll push through it.
So my goal is to still pushthrough it, not have any of you
fall asleep, despite yourtendency and not to have anybody
leave,
Dr. Michael Koren (00:39):
so that's where you learn the truth.
I'm a time hog.
So go for it, Mitch.
Dr. Mitchell Rothstein (00:50):
All right.
So when we talk about COPD,what does it stand for?
So chronic obstructivepulmonary disease?
Chronic means it's there allthe time, doesn't go away.
It may get better, maybe get alittle worse.
Obstructive means that there'sairflow obstruction.
I'll go into that in just asecond Pulmonary.
It's affecting the lung tissueand disease that there's damage
to that organ.
So why don't you take this one?
Dr. Michael Koren (01:09):
Yeah, so we always like to have input from
the audience and we always liketo say that there's no free
lunch.
You have to work for it.
So, with that in mind, which ofthe following statements is
true about COPD?
Most cases of COPD are causedby inhaling pollutants, Fumes,
chemicals and dust found in manywork environments are
contributing factors.
Genetics can play a role if anindividual's development of COPD
(01:33):
, even if the person has neversmoked or all of the above, Okay
.
You see, we have a really smartaudience here, right, so we can
just skip to the end.
There we go, okay.
Dr. Mitchell Rothstein (01:44):
And here , which of the following is
false?
This is one of those SATquestions.
You have to read it carefully.
Which is false?
Most people with COPD have notbeen diagnosed.
COPD patients may have had ahistory of asthma.
Most COPD patients do not havebreathing tests that prove that
they have COPD patients do nothave breathing tests that prove
(02:07):
that they have COPD.
Copd patients should notreceive vaccines for RSV, covid
or flu, or most COPD patientsdie from heart disease.
So one of these is false, whothinks one is false, who thinks
two is false, who thinks threeis false, who thinks four is
false and who thinks five isfalse?
(02:27):
All right, well this is prettygood, you guys.
So obviously Did you sell theanswers to this test beforehand.
Announcer (02:34):
Well, it's obviously an educated group.
I mean, they knew they werecoming for a COPD talk.
Dr. Michael Koren (02:37):
There we go.
They were prepared.
Dr. Mitchell Rothstein (02:39):
Yes, it's a subselect group.
Announcer (02:41):
So we know that COPD is the fourth leading cause of
death in the United States,trailing accidents.
So heart disease is first,cancer is second, then accidents
is third and COPD is fourth.
But we're gaining ground,especially since there's a
little delay in the developmentof COPD from when people
actually stop smoking or haveinhalational injuries.
So we're still starting to seethat tsunami from the 70s and
(03:04):
80s when people really startedto stop.
We know it's progressive.
It affects more than 14 millionpeople in the United States
that we have diagnosed.
We think there's probably atleast twice as many that have
COPD that are undiagnosed.
It's chronic inflammation ofthe airways and the lung tissue
results in reduction in airflow,which makes it then difficult
to breathe.
(03:24):
That work of breathing hasincreased and we've realized
over the last 20 years thatthere's really two different
kind of phenotypes of COPD.
There's a phenotype that hasjust inflammatory cells in their
lungs and then there's aphenotype that has inflammatory
cells and eosinophils like anasthma component in their lungs.
So this is an interesting part.
Dr. Mitchell Rothstein (03:47):
Yeah, you showed this to me earlier
today.
This is fascinating.
So this is NIH funding from 2015for different diseases and then
the deaths per year from thosediseases.
So the NIH funded Parkinson'sdisease to the tune of 146
million.
There were 28,000 deaths.
Alzheimer's disease got 589million for 110,000 deaths.
(04:09):
Liver disease got 616 millionfor 50,000 deaths.
And HIV got $3 billion for6,500 deaths.
And COPD was funded 37 million,far below any of these others,
and there were 150,000 deaths inthose years.
Dr. Michael Koren (04:29):
Right, and so a lot of this is probably
driven by politics is you haveadvocacy groups that go out and
get the government to spendmoney in their disease of
concern.
Dr. Mitchell Rothstein (04:40):
And as well as there's a little kind of
a social aspect to it too.
People that smoke get COPDlargely and there's kind of this
is a self-induced disease andpeople are less happy about
funding those quote types ofdiseases.
Dr. Michael Koren (04:55):
Yeah, people who smoke can make the argument
that they're paying a lot oftaxes every time they buy
cigarettes and their tax moneyshould go to use to figure out
what to do about it.
And the government wasinstrumental in getting them
addicted to nicotine.
There we go,all right.
Announcer (05:10):
So, speaking of smoking, we know that cigarette
smoking in the United States theleading cause of COPD.
There's 5,000 chemicals incigarette smoke, including
formaldehyde and benzene thatyou're inhaling into your lungs
and all these cause inflammationand destruction of the lung
tissue, as well as inflammation,mucus production in the airways
(05:30):
, leading to these two kind ofphenotypes of COPD.
One is called an emphysematouspatient and those are patients
we used to call them pinkpuffers.
They have hyper-expanded lungs,they're always short of breath,
their blood oxygen level isrelatively well-maintained.
And then the chronic bronchiticare the patients that are not
(05:52):
tall and thin, they tend to beheavier set, they produce a lot
of mucus and they're more proneto having low oxygen levels.
But those two kind ofphenotypes have also fallen out
of favor over the last few years.
There is a dose-responserelationship.
We think that.
(06:15):
Don't quote me on this, butmost people, if they smoke for
less than 20 years, have a verywell 20-pack years that's one
pack a day for 20 years have amuch lower risk of developing
COPD than people who smoke morethan 20-pack years.
One pack a day for 20 years.
Now there are people who arehighly sensitive to the toxins
in cigarette smoke and if theysmoke for five years they can
(06:35):
develop COPD.
So it's not a hard and fastrule.
And one way to gauge kind ofwhere you are in terms of your
lung age is if you're 50 yearsold and you've been smoking for
30 years a pack a day.
You take your 50 years old andyour pack years divided in half,
which would be half of 30, 15.
So you're a 50 year old with a65 year old lung.
(06:57):
That's kind of one easy way tokind of think about it.
Dr. Michael Koren (07:01):
It's interesting Is there any time
after you stop smoking whereyour risk of COPD goes back down
to everybody else's risk?
Announcer (07:08):
Well, the problem with COPD is the C part, the
chronic part.
So once you have COPD your lungfunction is permanently damaged
, and so far we haven't beenable to reverse that, not with
at least the current medicinesthat we've been using for the
last 30 years.
Dr. Michael Koren (07:26):
Okay, all right.
So another audience questionAir pollution can contribute to
the development of COPD True?
False?
I need to listen to theMedEvidence! podcast to know the
correct answer.
Dr. Mitchell Rothstein (07:41):
I think that's three right.
Dr. Michael Koren (07:44):
We should have put one in three as our
actual answer, but yes, true.
Dr. Mitchell Rothste (07:48):
Absolutely .
I think the most obviousexample of this recently is
California and all the wildfiresthey had there.
That's all air pollution.
There's probably been moreparticulate matter and toxins
released into the air inCalifornia in the last three
months since the beginning ofrecorded time, so air pollution
definitely affects thedevelopment of lung damage and
(08:11):
can exacerbate COPD.
Dr. Michael Koren (08:13):
And I think there's a broad way of defining
environmental exposures and airpollution.
Announcer (08:19):
Absolutely so.
Actually, you know what?
The most common cause of COPDin the world is the use of
biomass fuels.
So what's a biomass fuel?
In sub-Saharan Africa, whenthey're cooking, they use animal
dung as their fuel and theycook inside an enclosed area and
(08:42):
they inhale all those fumes.
So that's the leading cause ofCOPD in the world.
Not that many people can affordcigarettes, but they all have
to eat and they all cook theirfood, and that's the biggest
determinant of COPD in the world.
Occupational hazards we knowthat the burn pits that our
soldiers were exposed to inAfghanistan that certainly has
(09:04):
caused COPD in a number of themand any other activity that's
involved with fumes or volatilecarbon odors can all lead to
COPD and damage of your lungs.
You have to remember anythingyou can smell, those molecules
are being filtered by your lung.
(09:26):
So when you smell something bad, those same little molecules
are traveling into your lung andgetting embedded in your lung
tissue and then have to beremoved.
So we're always filteringpollutants out of the
environment in order to keep ourlungs healthy.
Dr. Michael Koren (09:40):
So your take-home advice is that if
you're using dung for cookingpurposes, that you should open a
window.
Dr. Mitchell Rothstein (09:46):
Open a window Well aerated.
Dr. Michael Koren (09:50):
Okay, so talk about genetics.
Dr. Mitchell Rothstein (09:52):
So we do know that there's at least two
genetic diseases that areclearly associated with poor
pulmonary function in the formof this chronic obstructive lung
disease.
One is alpha-1 antitrypsindeficiency.
That's an autosomal recessivegene that's passed on from your
parents.
There are different forms ofthis disease, all worldwide.
(10:18):
There's different alleles thatmake up the alpha-1 antitrypsin
genome.
The ZZ part of the allele isthe most devastating, and what
alpha-antitrypsin does is itreduces the breakdown of lung
tissue.
Trypsin is an enzyme that chewsup lung tissue.
Antitrypsin prevents it fromdoing that.
(10:39):
If you don't produce theantitrypsin, then your lung gets
chewed up.
The other genetic disease iscystic fibrosis.
That clearly causes COPDthrough mucus production and
lung damage.
And then, since the humangenome project was finished, we
know that there's associationswith some other genetic loci
that are associated withincreased risk of COPD
(11:01):
development.
It doesn't mean you'redefinitely going to get them we
don't routinely screen for thembut we know that, like
everything else in this world,there's a bell-shaped curve of
sensitivity to bad things thatcan happen to you, and lung
damage is one of them.
We also know that if your lungshave been damaged from any
(11:21):
reason and in the prebiotic area, we knew that repeated
infections, especially inchildren, can lead to permanent
lung damage.
Basically, your lung reachesits maximum level of function at
about the age of 20 to 25.
Coincidentally, that's whenmost of your elite athletes are
reaching their peak potentialtoo.
(11:42):
And then, after about age 25,we all start to lose function
for the rest of our lives.
Now we lose that function atdifferent rates.
So an average person is goingto die from something other than
loss of lung function at theage of 90.
They'll still have plenty oflung function left, but if that
(12:03):
curve takes a steep downwardtrajectory after being exposed
to infections or constantexposure to pollutants and
cigarette smoke, your curve isgonna be steeper, and you don't
wanna run out of lung functionbefore you run out of life.
Dr. Michael Koren (12:19):
Good way to think about it.
So how about aging?
Announcer (12:23):
Yeah, and this is what I was talking about.
As we get older, we all loselung function.
This may not be that meaningful, but an average person
non-smoking, otherwise healthyloses about 20 cc's of forced
vital capacity lung function ayear and I'll go over that in
just a second.
But that can increase to over100 cc's.
(12:43):
And then in patients that haveCOPD, when they have an
exacerbation of their COPD andrequire hospitalization or other
medicines than their usualmaintenance medicines, they lose
a lot more.
They could lose up to 150 or200 cc's just from that one
episode.
And the thing about COPD isit's not like asthma.
(13:04):
When you get better from COPDyou don't go back to where you
were.
You go back a little bit, butyou're worse than before you had
the exacerbation and I'm goingto talk about this repeatedly.
One of our goals in treatmentnow is to make sure that people
with COPD don't have thoseexacerbations.
Dr. Michael Koren (13:24):
Okay, so to an audience question here.
Which of these is a commonsymptom of COPD Sneezing,
shortness of breath, bad breath,hiccups or a need for an oxygen
tank?
So who says sneezing, who saysshortness of breath, bad breath,
(13:46):
hiccups, need for an oxygentank?
All right, well, I guess thecommon one would be shortness of
breath.
Dr. Mitchell Rothstein (13:54):
That is the common one.
We've got a stacked audienceand nobody's asleep yet.
Nobody's left yet.
and we're more than halfway done.
So we're going to get there.
So the shortness of breath.
You know, when people come tosee a cardiologist or a
pulmonologist, one of the mostcommon complaints we get always
is that they're short of breath.
So when they come to see Dr.
(14:14):
Koren, he says, well, it's notyour heart, it must be your
lungs.
And when they come to see me, Isay, well, it's not your lungs,
it must be your heart.
And so what we want to do isfigure out which one it really
is.
And how does lung disease makeyou short of breath?
And that is the most commoncomplaint.
And if you're seeing apulmonary specialist, he's
probably giving you a littlequestionnaire called an MMRC,
(14:36):
which is a kind of like the NewYork heart classification.
It says I get short of breathwhen I'm doing daily activities,
when I make the bed, when Iwalk one flight of stairs, and
it helps us kind of gauge thedisability of the patient based
on their answer to that and thelevel of their lung function.
Dr. Michael Koren (14:54):
Yeah, and a couple of people raised their
hand for an oxygen tank, but Ithink it's fair to say that the
people that need to walk aroundwith an oxygen tank are a very
small percentage of all peoplewith COPD.
Dr. Mitchell Rothste (15:03):
Absolutely ,
is that fair to say?
Dr. Mitchell Rothstein (15:05):
Yeah.
So it's when people requireoxygen therapy and I'm going to
show you why they do that injust a second but that means
that their lung function hasreally deteriorated quite a bit
and that you're clearly at apoint where you have to be
careful about everything.
Dr. Michael Koren (15:20):
And that's maybe one or two percent of all
people with COPD.
Dr. Mitchell Rothstein (15:23):
Yeah, less than 5%.
Dr. Michael Koren (15:25):
Okay.
Okay, how about cough?
We talked last month aboutcough and, excuse me, we're
doing speaking of cough, butwe're doing some research right
now, because cough is a verycommon symptom.
You and I were just talkingabout how many coughs is normal
versus how many coughs a day isabnormal.
(15:46):
It's one of those things thatonly crazy, nerdy people like us
think about, but it's importantbecause this can be disabling
for some folks Absolutely, andthere's a lot of reasons people
get cough, but is COPD one ofthem.
Announcer (15:59):
Absolutely so.
Part of COPD is chronicinflammation.
With that chronic inflammationyou have chronic mucus
production and that mucus endsup in your airways.
Those airways are innervated bynerves that are connected to
your brain that induce thatcough reflex.
Additionally in your lungs youhave something else, receptors
(16:20):
that are called J-receptors orstretch receptors, and people
that have COPD and have damaged,over-inflated lungs, those
J-receptors are activated alsoand they cause that cough urge.
So not everybody.
You don't have to choke on achicken sandwich to cough.
You can cough, because there'sthings going on in your lung
tissue chronically all the timethat are activating those nerves
(16:41):
.
Dr. Michael Koren (16:42):
And so Dr.
Rothstein and I were talkingabout the fact that there are a
lot of people out there thatcough more than 15 times an hour
, and it's not clear why they dothat.
Right, they cough less whenthey're sleeping, of course, but
when they're awake you mayclear your throat a little bit,
just like a little cough or justa more prominent cough, and if
you have that issue, there's aphone number you can give us a
(17:04):
call.
We can get you involved in someof the research, and this is
the benefit to the patients isthat we'll actually put a
monitor on you to see howfrequently you cough.
So one of the crazy things thatwe do in research is really
analyze the type of problemspeople have, and you may or may
not get in the study, but you'llget the information about your
cough frequency.
Dr. Mitchell Rothste (17:22):
Absolutely .
It's a fascinating study andit's the first study that's
looking at a drug indicated forthis specific indication.
So there's no medicine outthere now that's approved for
chronic cough.
You know we give peoplenarcotics to slow down their
cough, benzonatate to slow downtheir cough.
None of those have been reallyproven to work effectively.
(17:43):
And this is attacking this kindof neurogenic reflex that we
know is active in people, andwe're not including copd
patients in the study right now.
First we want to see if it workson people that don't have
intrinsic problems with theirlungs
Dr. Michael Koren (17:57):
But the nice part of the research process, of
course, is we'll help you sortit out right while you have, why
you may be having that orsomebody you know may have that.
All right, so let's talk aboutthe grim signals now of COPD.
Dr. Mitchell Rothstein (18:09):
So you know, and when we look at
patients with COPD we kind oftry to match the treatment to
their symptoms, not so muchtheir numbers.
The numbers, these breathingtests we use in COPD, are
basically to make a diagnosisand then, based on symptoms, is
how we treat people.
And the symptoms that we'reprimarily looking at are listed
(18:30):
here.
It's fatigue, it's shortness ofbreath, it's increased
shortness of breath withactivity, it's wheezing and
mucus production, chesttightness and, like I said about
COPD, it's a chronic diseaseand over time it's going to get
worse.
How quickly it gets worse, youknow, nobody knows until we're
following people over time it'sgoing to get worse and can
(18:52):
measure their symptoms and theirbreathing tests and see what
kind of trajectory on.
But we know that if you'resymptomatic from COPD now left
alone, it's not going to getbetter on its own.
Dr. Michael Koren (19:07):
So give us a little bit more insight into
exactly what your lungs do on aday-to-day basis.
Dr. Mitchell Rothstein (19:11):
Yeah, Well, this is important for me
because I always have to remindmyself and it's always, I think,
difficult for people that haveCOPD or don't have COPD as to
what our lungs actually do.
So your lungs have twooperational details.
Number one is to ventilate, soit moves air in and out of your
(19:32):
lungs and it does it throughthese airways.
So you can see the mainwindpipe there, your trachea,
and then it divides in half intoyour we call main stem bronchi,
and then those airways divide23 more times until it reaches
the end, aviolus, where theperfusion part starts.
(19:52):
And if you line up all thoseairways, that's 1500 miles of
airway that we each have in ourlungs.
So you can imagine if you havesome mucus in all 1500 miles,
it's going to increase the workof getting air past all that
mucus.
And the other thing that happensis only in the main windpipe
(20:13):
and those bronchi that come tothe top are the airways
supported by cartilage.
After that main division, theairways are just muscular tubes,
so they're like blood vesselsalmost.
They can be easily compressed.
If you breathe in real fast orbreathe out real fast, they
expand and collapse and that cancause problems with the air
(20:34):
movement too.
So the other thing that yourlung does is this perfusion and
if you go to the next slide,
there's one other thing you'releaving out.
There are two nice pillows, sothat the heart is comfortable in
the middle.
Well as a lung specialist you know I
know the heart only has onepurpose and that's to pump blood
to the lungs.
So as a cardiologist Dr.
(20:55):
Koren has a differentperspective on it I see it as
taking up valuable lung room.
So then, once you get down toall those airways, what they end
in is something called thealveolus, which you see here,
and these are tiny little bubblesacks and every alveolus has a
blood vessel that you can see inthis diagram here, that kind of
(21:17):
wraps around it, and there areabout three or four million of
these little bubble sacks ineach lung and if you spread all
those out it'd be 75 squaremeters of bubble sacks, a tennis
court of bubble sacks that allthese blood vessels wrap around.
And the blood that starts tocome in and wraps around the
(21:38):
lung doesn't have any oxygen,has lower oxygen levels in it
and high carbon dioxide levels,because that's all your body is
Metabolizing.
So now the bloods taking thisextra carbon dioxide and lower
oxygen level to your lungs forthe perfusion.
Part of this now Interestinglyand I'll be real quick with this
carbon dioxide is a much morediffusible gas than oxygen is.
(22:01):
So from the time that Bloodhits that alveolus, the carbon
dioxide comes out very quicklyand about the first 15% of that
transit time around the alveolusthe oxygen takes longer about
75% of the transit time to getall the oxygen into the blood.
So in the alveolus you've gotthe carbon dioxide coming out of
(22:23):
the blood, the oxygen from thealveolus going into the blood,
and then you blow it out.
So every minute you'rebreathing in and out about six
liters of air and every minuteyou're pumping about five liters
of blood.
And there's a little overlap onthe lung side because we know
the heart's not that efficient,so you have to kind of make up
(22:44):
for that problem
Dr. Michael Koren (22:48):
the anti-cardiac Society will be
calling you.
You'll be getting a letter fromour attorney.
Dr. Mitchell Rothstein (22:53):
So the importance of this is this is
where the gas exchange occurs,so you can see if you're
damaging this, if these bloodvessels are getting squeezed off
or if the alveolus is gettingdestroyed the carbon dioxide.
Usually there's enough roomleft for the carbon dioxide to
get out, but the oxygen doesn'talways have time to get in and
(23:14):
then people need to be onsupplemental oxygen.
If you've lost your ability toget rid of carbon dioxide and
that level's going up in yourbloodstream, we call that
hypercapnic respiratory failure.
That's a much more seriousadvanced condition.
Dr. Michael Koren (23:30):
All right.
So another audience questionhere which of the following is a
test that doctors use todiagnose COPD?
One spirometry, twoplethysmography.
Three pulse oximetry.
Four tomography or five, all ofthe above.
Dr. Mitchell Rothstein (23:50):
Yeah well, spirometry is the test
that we use to diagnose COPD.
We do pulmonary function teststhat include a lot of this other
stuff.
I don't have time to explainbecause Dr.
Koren took up a long time.
That's fine, so we'll go aheadwith spirometry.
Dr. Michael Koren (24:04):
I'll give you two minutes but explain that a
little bit more, because peoplethought it was all the above,
but when you really look at thequestion in terms of the formal
diagnosis of COPD, it's a littlebit different.
So go ahead.
Dr. Mitchell Rothstein (24:17):
So spirometry we're going to show
you a slide about.
Plethysmography is ameasurement that we use to look
at lung volume.
So we have different volumesthat we associate with our lungs
.
So when I take in a deep breathfrom resting, so I have a
normal exhalation and then Itake a deep breath in from that
point, that's my inspiratorycapacity.
(24:39):
That's one volume.
If I blow all the air out of mylungs until no more air can
come out, that's my vitalcapacity.
But even at the end of thatthere's still some air left in
my lungs and that's called theexpiratory reserve volume.
And then looking at differentvariations on how that air comes
(25:00):
out is part of the spirometricanalysis that we use to diagnose
COPD.
Pulse oximetry measures youroxygen level in your bloodstream
.
It's got a little bit of errorinvolved in it.
For a normal person at sealevel it's about 94% plus or
minus 2%.
As you go up and there's lessoxygen, that number obviously
(25:23):
comes down.
Tomography we don't use so muchin breathing tests or in lung
evaluation.
So it's really the first threethat are associated with lung
testing and spirometry is themost important for diagnosing
obstructive lung disease and whydon't we go on to the next one?
So, obstructive lung disease,there's really two types.
(25:45):
There is COPD, and then there'sasthma, and then there's this
condition called an overlapsyndrome that has a lot of
characteristics of both, butspecifically with COPD, we
measure the total amount of airthat I can blow out from one
deep inhalation.
I blow the air out as fast as Ican and then at six seconds, if
(26:08):
I last that long, that totalamount of air that comes out is
called the forced vital capacity.
Of that, the part that comesout, why don't we go to the next
slide?
And I can show them better.
So of that, if you look at thistop curve, the lines going up
right, right and I'm blowing airout, that's the forced vital
capacity.
If you look at the amount ofall that air that comes out the
(26:32):
amount that came out in thefirst second, and you can see
that most of it, about 80% orbetter, is coming out very
quickly, right at the beginning.
Dr. Michael Koren (26:41):
This is a second, I take it right?
Dr. Mitchell Rothstein (26:43):
Right Time in seconds on the bottom,
right, right, and so as that,all that air that comes out,
most of it comes out veryquickly at the beginning.
So when we do this spirometrytest we look at your spirometry
and we say how much of all theair that came out came out in
the first second and if it'sless than 70% that's called
(27:04):
obstructive lung disease.
And when it's less, that curveon the top, mike kind of
flattens and doesn't rise up asquickly as it did on the normal
patient.
Now the exception to this is ifyou have obstructive lung
disease, meaning that FEV1 wasless than 70% of the total, and
then we give you like an inhalerand it goes to better than 70%,
(27:27):
you have asthma, you don't haveCOPD.
So this is the test that tellsus in large groups of people
whether or not they have COPD.
So an FEV1 less than 70%.
And the nice part about this isyou're your own control.
You know we're not comparingyour test to a lot of other
people's tests.
For this FEV1 percent test it'syour total versus the amount
(27:51):
that came out in the firstsecond and if that's reduced too
low then you have COPD.
If it doesn't improve.
Dr. Michael Koren (27:56):
So, to paraphrase what you just said,
just and connect it with thepicture so if this is what your
spirometry looks like, you usean inhaler and then it starts
looking like that
Dr. Mitchell Rothstein (28:06):
Correct.
Dr. Michael Koren (28:06):
Then that's asthma, not COPD,
Dr. Mitchell Rothstein (28:08):
Correct.
Announcer (28:08):
If it returns to normal.
Dr. Michael Koren (28:10):
Thank you.
Dr. Mitchell Rothstein (28:12):
So these are kind of the after effects
of what COPD does on a chestx-ray.
So this is a normal chest x-rayon your left and you can see
the heart silhouette.
The patient is looking out atyou, right shoulder, left
shoulder, and you can see theheart silhouettes there.
There are where that green andpurple arrows are are the blood
vessels in the heart, in thelungs.
(28:34):
You can barely see them, andthen these curved things on the
bottom are your diaphragms.
So when we breathe in, webreathe in under negative
pressure, we suck air in.
So when we breathe in, weexpand our diaphragm so they
contract and they go down.
That creates negative pressurein our chest and we suck the air
in.
Now, when patients develop COPD,they have this obstructive
(28:56):
problem to airflow and they getthe air never fully exhaled and
they keep hyperinflating.
They keep getting more and moreair stuck in their chest and it
leads to an x-ray that lookslike that.
So you can see where thediaphragm should have been,
where those lines are and wherethey are now.
You can also see the bloodvessels that are going into the
(29:18):
lungs now are very prominentbecause the lung tissue has been
destroyed and the heart ishaving a difficult time pumping
all that blood to the lungsagain.
So those blood vessels tend todevelop to increased pressure.
So you can experience thisright now at your table If you
take a breath in and then try totake another breath on top of
(29:41):
that.
That's how that person feels allthe time.
Every breath is a consciouseffort.
They're short of breath all thetime time.
They don't have that room fortheir diaphragms to contract
anymore and go down.
So the differences between COPD.
In general we know that both ofthem can have swollen, narrow
(30:01):
airways.
We know that in asthma, like wewere saying, if you use that
inhaler and the breathing testgoes back to normal, we call
that reversibility.
That happens much more often inasthma.
Patients with COPD may have aresponse to bronchodilators but
they never go back to normal orelse we'd call them asthmatics.
We know that people with asthma, their symptoms can come and go
(30:22):
, they can have flares of asthma.
With COPD that sense ofshortness of breath tends to be
more constant.
In asthma because their airflowcan go back to normal.
We know that that's true.
In COPD, it never goes back tonormal.
Asthmatics tend to have ayounger age of onset than people
with COPD, who typicallydevelop the disease in their 40s
(30:42):
, 50s and upward.
But you can develop asthma atany age as well, and we know
that the allergic background ismuch more prominent in
asthmatics than it is in COPDpatients.
But we're learning that thereis some type of this type 2
inflammatory allergic responsein COPD patients that may have
more significance than wethought.
(31:06):
So the goals of treatment withCOPD are we can't cure it.
We want to slow down theprogression and we want to
improve patients' abilities toengage in activities of daily
living.
And the key to COPD control isreducing these exacerbations,
(31:27):
because if we can reduce thosebig drops in lung function, we
think that will improve qualityof life.
So how do we do that right now?
So when I was in training, mostof the things I'm going to talk
about weren't even in the realmof treatment options.
But now we know the best thingyou can do is stop smoking.
(31:50):
That's going to help reducethat fall in your lung function
and reduce cardiovasculardisease and everything else that
goes along with it.
We have the slew of medicinesthat we use in COPD Pulmonary
rehab, this exercise programthat anybody with symptomatic
COPD should go through.
So symptomatic means if youhave COPD and you're short of
(32:13):
breath, even if you haven't beenhospitalized, you want to go
through a pulmonary rehabprogram.
We know that that improvesquality rehab program.
We know that that improvesquality of life.
We know it reducesexacerbations and we know it
reduces hospitalizations andshort term it has a reduction on
mortality as well.
Supplemental oxygen if neededand like Dr.
Koren was saying, it's lessthan about one.
(32:35):
Two percent of our patientswith COPD need supplemental
oxygen.
But if you need it it isassociated with increased
quality of life and increasedlife expectancy.
We've developed non-invasiveventilation which is kind of
like you know a CPAP.
You know CPAP for patients withsleep apnea.
Well, we have a CPAP that cankind of act like a ventilator to
(32:58):
help people breathe at night.
That can reduce that work ofbreathing so people can sleep
through the night if their COPDis that progressive.
We have also been doingsurgeries on lungs.
You've probably heard of lungvolume reduction surgery.
So if people have emphysema,these big blebs in their lungs,
we know that we can take thebleb out and that allows normal
(33:22):
lung that's left over tore-expand and to function more
normally and that can improvetheir sense of dyspnea and
quality of life Without doingsurgery.
In one of those tiny littleairways we can put a one-way
valve that kind of shuts theblood flow and the oxygen off to
that part of the lung and thatlung will collapse, essentially
(33:42):
doing an autobulectomy.
The rest of the lung willexpand and improve quality of
life and send some dyspnea there.
And then we've also done lungtransplantation in patients with
primarily unilateral diseaseand primarily of an
emphysematous type, but that'salso been one of the surgical
approaches as well.
Dr. Michael Koren (34:02):
I haven't heard as much lately about
volume reduction surgeries as Idid 20 years ago.
Is that falling out of favor alittle bit?
Announcer (34:08):
It's falling out of favor because of the
endobronchial valves.
Instead of, you know, crackingyour chest open, we can down in
the bronchoscopy suite, put thatvalve in and get almost the
same result.
Dr. Michael Koren (34:18):
Got it.
Dr. Mitchell Rothstein (34:23):
And then there's clinical trials.
So, and then the clinical trialsthat are going on are
addressing Medications that willimprove lung function, delivery
of those medicines to improvelung function, as well as a
(34:43):
bunch of anti-inflammatorymolecules that have just come
out in the last decade that arehaving surprising results in
COPD patients in terms ofhelping them improve lung
function, reducehospitalizations and reduce
exacerbations.
So the old traditionalmedications that we used in COPD
are basically divided up intothree groups.
We have the beta agonist, whichis like albuterol that we use
(35:07):
in asthma.
They tend to be short.
There's one group that tends tobe short-acting that lasts a
couple, three hours, and thenlong-acting that can last 12 to
24 hours, and these medicineswork by increasing this mediator
called cyclic AMP in the musclecell, which causes these muscle
(35:27):
tubes to relax and they getbigger, and it's been very
effective and has a relativelyshort onset of action.
We call them rescue medicines.
When it's the short-actingvariety, it can give people
relief within minutes.
And then the next major classis these go to the next slide.
(35:47):
Are these anticholinergic agents, or we call them LAMAs,
anti-muscarinic agents, andthey're largely used in patients
with COPD.
Ipitropium is one that's beenout for about 20 years.
It's now finding a place in theuse and treatment for asthma as
well.
And instead of activelydilating the airways, what these
(36:11):
anticholinergic medications dois they interfere with the
ability of the airways toconstrict, so they relax them,
but they don't actively relaxthem.
They're very effective.
Also, they come as ashort-acting medication and a
long-acting, a LAMA medicationas well, and there's a bunch of
different names for thedifferent products there.
(36:31):
I won't go through them becauseMike used up all my time.
Go on to the next slide andthen we have this group of
medicines called inhaledcorticosteroids.
So when I did my training backin the well, whenever, the first
use of inhaled corticosteroids-
Dr. Michael Koren (36:49):
Which century was that?
Dr. Mitchell Rothstein (36:53):
-so it just coming out onto the
marketplace and it was used.
We were using it in patientswith asthma the marketplace and
we were using it in patientswith asthma and all of a sudden,
instead of having an ICU fullof asthma patients on
ventilators and with a very highdeath rate, nobody was showing
up to the ICU anymore becausethese inhaled corticosteroids
(37:13):
were great at reducing theinflammation in the airways in
these asthmatic patients and itreduced those exacerbations and
the need for them to seekhospitalization.
So we translated that success inasthma patients to patients
with COPD and I think you'veseen widely advertised on TV and
(37:36):
probably some of you may beeven using them.
We kind of combined all thesegroups of medicines together and
now kind of standard therapy wecall it triple therapy for
patients with COPD is along-acting beta agonist, that
one that actively dilates theblood vessels, a long-acting
muscarinic agent, which is onethat prevents the airways from
(37:59):
constricting, and an inhaledcorticosteroid.
And those can be very expensiveand we're not sure if it's
really beneficial in all COPDpatients.
One of the interesting thingsthey found that when they looked
at patients with COPD thepatients that used inhaled
corticosteroids had decreasedacute myocardial events over a
(38:19):
decade but, they had increasedrisks of pneumonia and upper
respiratory tract infections.
So we're trying to sort that out.
So inflammatory versuspro-infection.
Dr. Mitchell Rothste (38:30):
Absolutely
Dr. Michael Koren (38:31):
Interesting.
Dr. Mitchell Rothstein (38:34):
So these are the different kind of
combinations SABA is ashort-acting beta agonist used
with a LABA, a long-acting betaagonist, and a LAMA, a
long-acting muscarinic agent.
And then you can use the tripletherapy the LABA, LAMA, and ICS
.
Now these are all given byinhalation and one of the
(38:55):
problems with COPD is you can'treally breathe that well to
begin with.
So part of the problem with ourtherapy is if you can't actuate
the device or open the deviceand inhale deep enough to get
the medicine to your lungs, itdoesn't work as well if you just
go and the medicine just goesinto the back of your throat.
(39:17):
So we have a bunch of goodmedicines for people, but a lot
of people have difficulty usingthem and I can tell you in my
practice, every time I saw apatient for follow-up that was
using inhalers, I asked them touse it in front of me just to
make sure they were doing itadequately, and 50% of the time
people would have their actuatorand they'd show me up, they'd
(39:38):
squeeze it.
It didn't even go in theirmouth and then they'd inhale and
you'd say, well, we went overthis, you know, three months ago
, and it takes a lot ofrepetition if you're not doing
it every day, it's a hard skillto kind of master.
So over the last 15 years we'verealized that there's other
inflammatory components to COPDand not just treating the airway
(40:01):
, opening and closing.
Among those are these a bunchof inflammatory cytokines and
alarmants.
They have a huge number ofdifferent names and it's just
more and more.
The more I read on this, themore confused I get as to which
pathway what's interfering with,the more confused I get as to
which pathway what's interferingwith.
Daliresp or roflumilast came outas a phosphodiesterase
(40:23):
inhibitor type 4.
So we have about six of thesephosphodiesterase inhibitor
types.
Two of them are pertinent toyour lungs, four is the most
common, but there's also three.
And what phosphodiesterase doesis it inhibits the breakdown of
cyclic AMP, which causes theblood vessels, the airways, to
(40:45):
dilate.
So these medicines reduceinflammation in the airways and
they cause them to dilate alittle bit.
More, recently Ensifentrine,came out and that's a PDE3 and 4
inhibitor and it seems to bemuch more potent than Daliresp
has been and that seems to notonly improve lung function but
(41:08):
also reduce exacerbations andhospitalizations.
And Ensifentrine and Dupilumab,which is a monoclonal antibody.
You've probably it's calledDupixent.
You've probably seen itadvertised for eczema and for
asthma.
We now know that that medicineis also effective in COPD
patients.
(41:28):
But there's a certain type ofCOPD patient that that's
important for, and that'spatients that on their blood
counts have high eosinophiliclevels.
Like I said before, the allergyis more common in asthma than
it is in COPD, but we know thatthere's patients with COPD that
have that allergic component andthey seem to respond to this
(41:48):
quite nicely.
Dr. Michael Koren (41:50):
Yeah, I think you told me this anecdote about
how important it is to actuallywatch patients use the inhalers
.
I think you told me about thisanecdote where you asked
somebody to do that.
The person sprayed it in theair and then put their face in
the mist.
So it's more than a trivialpoint.
Dr. Mitchell Rothstein (42:08):
I would say that in my practice and I
practiced for over 30 years thatmy patients with COPD, one that
actuated and inhaled properlywas about 50%, and then of the
people that did that properly,the people that could get a deep
enough inhalation in to reallymaximally benefit from the
medicine, was about 75%.
(42:30):
So a lot of these medicineslose their power Now.
Interestingly, some of thesemedicines are now available by
nebulizer and we're going tohave a study, hopefully in the
next few months, that is, usinga nebulizer just twice a day,
using these long-acting products, so that people will actually
get a benefit from theirmedicine.
Dr. Michael Koren (42:48):
That's interesting, yeah.
Dr. Mitchell Rothstein (42:49):
So among the biologics, Dupixent isn't
the only monoclonal antibody outthere that's looking
specifically for these eithereosinophilic type or
non-eosinophilic type COPDpatients.
There's a list here of theothers, some of their target
compounds, and they're kind ofgoing through this trying to
find out which medicine is rightfor what we call them phenotype
(43:12):
, either an eosinophilic or anon-eosinophilic dominant
patient with COPD, and at leastwith the eosinophilic group we
know that the depiction ishaving a marvelous effect on
helping them reduceexacerbations.
Dr. Michael Koren (43:26):
Yeah, and if you want to impress your friends
at a cocktail party, you'llnotice that all the monoclonal
antibodies end with MAB.
So if somebody has aninjectable drug they're using
and you can tell them if it's amonoclonal antibody or not just
by looking at it.
Okay, well, now somethingimportant.
Yeah, COPD in thecardiovascular system Go ahead.
Dr. Mitchell Rothstein (43:46):
Patients that have COPD you know it's
the people that smoke a lot tendto run the risk of heart
disease.
So we know that.
You know we're dealing withpatients that often have two
comorbidities they have lungdisease and they have heart
disease.
We know that if you have anexacerbation of COPD, you're
going to be at risk for havingan acute myocardial or
(44:07):
cardiovascular event as wellstroke or heart attack and that
as COPD progressed, when thoselittle bubble sacks, alveoli get
destroyed and the blood supplygets destroyed and the heart is
still pumping that five litersper minute through the heart,
but it's a smaller vascular bedthose blood vessels are under
increased pressure and thatleads to pulmonary hypertension,
(44:30):
which then causes moreshortness of breath.
An interesting fact, too, isthat if you lose 10% of your
forced vital capacity, your riskof having an acute myocardial
event increases by 10%.
Dr. Michael Koren (44:42):
Interesting I had not heard that statistic.
Dr. Mitchell Rothstein (44:45):
Yeah, so pulmonary rehab, like I said,
should be a mainstay withanybody with a symptomatic COPD.
It's a supervised classroomexperience.
It teaches people how to dothings without putting their
respiratory system underincreased stress, as well as
increasing their stamina, and weknow that it improves quality
of life, reduces breathlessness,reduces exacerbation and
(45:08):
hospitalization rates.
Announcer (45:09):
Thanks for joining the MedEvidence! podcast.
To learn more, head over toMedEvidence.
com or subscribe to our podcaston your favorite podcast
platform.
Welcome to the MedEvidence! podcast.
This episode is a rebroadcastfrom a live MedEvidence!
presentation.
Dr. Michael Koren (00:06):
I'm really excited to learn about COPD
chronic obstructive pulmonarydisease and you've been spending
your whole career as an experton this and I don't know anybody
more knowledgeable, so let'srun through it.
Let's educate everybody aboutCOPD.
Dr. Mitchell Rothstein (00:22):
And just before I get started, Dr Koren
was very concerned that I hadtoo many slides and I was going
to take too long.
So he took up the first fiveminutes of my time and I said,
well, I'll push through it.
So my goal is to still pushthrough it, not have any of you
fall asleep, despite yourtendency and not to have anybody
leave,
Dr. Michael Koren (00:39):
so that's where you learn the truth.
I'm a time hog.
So go for it, Mitch.
Dr. Mitchell Rothstein (00:50):
All right.
So when we talk about COPD,what does it stand for?
So chronic obstructivepulmonary disease?
Chronic means it's there allthe time, doesn't go away.
It may get better, maybe get alittle worse.
Obstructive means that there'sairflow obstruction.
I'll go into that in just asecond Pulmonary.
It's affecting the lung tissueand disease that there's damage
to that organ.
So why don't you take this one?
Dr. Michael Koren (01:09):
Yeah, so we always like to have input from
the audience and we always liketo say that there's no free
lunch.
You have to work for it.
So, with that in mind, which ofthe following statements is
true about COPD?
Most cases of COPD are causedby inhaling pollutants, Fumes,
chemicals and dust found in manywork environments are
contributing factors.
Genetics can play a role if anindividual's development of COPD
(01:33):
, even if the person has neversmoked or all of the above, Okay
.
You see, we have a really smartaudience here, right, so we can
just skip to the end.
There we go, okay.
Dr. Mitchell Rothstein (01:44):
And here , which of the following is
false?
This is one of those SATquestions.
You have to read it carefully.
Which is false?
Most people with COPD have notbeen diagnosed.
COPD patients may have had ahistory of asthma.
Most COPD patients do not havebreathing tests that prove that
they have COPD patients do nothave breathing tests that prove
(02:07):
that they have COPD.
Copd patients should notreceive vaccines for RSV, covid
or flu, or most COPD patientsdie from heart disease.
So one of these is false, whothinks one is false, who thinks
two is false, who thinks threeis false, who thinks four is
false and who thinks five isfalse?
(02:27):
All right, well this is prettygood, you guys.
So obviously Did you sell theanswers to this test beforehand.
Announcer (02:34):
Well, it's obviously an educated group.
I mean, they knew they werecoming for a COPD talk.
Dr. Michael Koren (02:37):
There we go.
They were prepared.
Dr. Mitchell Rothstein (02:39):
Yes, it's a subselect group.
Announcer (02:41):
So we know that COPD is the fourth leading cause of
death in the United States,trailing accidents.
So heart disease is first,cancer is second, then accidents
is third and COPD is fourth.
But we're gaining ground,especially since there's a
little delay in the developmentof COPD from when people
actually stop smoking or haveinhalational injuries.
So we're still starting to seethat tsunami from the 70s and
(03:04):
80s when people really startedto stop.
We know it's progressive.
It affects more than 14 millionpeople in the United States
that we have diagnosed.
We think there's probably atleast twice as many that have
COPD that are undiagnosed.
It's chronic inflammation ofthe airways and the lung tissue
results in reduction in airflow,which makes it then difficult
to breathe.
(03:24):
That work of breathing hasincreased and we've realized
over the last 20 years thatthere's really two different
kind of phenotypes of COPD.
There's a phenotype that hasjust inflammatory cells in their
lungs and then there's aphenotype that has inflammatory
cells and eosinophils like anasthma component in their lungs.
So this is an interesting part.
Dr. Mitchell Rothstein (03:47):
Yeah, you showed this to me earlier
today.
This is fascinating.
So this is NIH funding from 2015for different diseases and then
the deaths per year from thosediseases.
So the NIH funded Parkinson'sdisease to the tune of 146
million.
There were 28,000 deaths.
Alzheimer's disease got 589million for 110,000 deaths.
(04:09):
Liver disease got 616 millionfor 50,000 deaths.
And HIV got $3 billion for6,500 deaths.
And COPD was funded 37 million,far below any of these others,
and there were 150,000 deaths inthose years.
Dr. Michael Koren (04:29):
Right, and so a lot of this is probably
driven by politics is you haveadvocacy groups that go out and
get the government to spendmoney in their disease of
concern.
Dr. Mitchell Rothstein (04:40):
And as well as there's a little kind of
a social aspect to it too.
People that smoke get COPDlargely and there's kind of this
is a self-induced disease andpeople are less happy about
funding those quote types ofdiseases.
Dr. Michael Koren (04:55):
Yeah, people who smoke can make the argument
that they're paying a lot oftaxes every time they buy
cigarettes and their tax moneyshould go to use to figure out
what to do about it.
And the government wasinstrumental in getting them
addicted to nicotine.
There we go,all right.
Announcer (05:10):
So, speaking of smoking, we know that cigarette
smoking in the United States theleading cause of COPD.
There's 5,000 chemicals incigarette smoke, including
formaldehyde and benzene thatyou're inhaling into your lungs
and all these cause inflammationand destruction of the lung
tissue, as well as inflammation,mucus production in the airways
(05:30):
, leading to these two kind ofphenotypes of COPD.
One is called an emphysematouspatient and those are patients
we used to call them pinkpuffers.
They have hyper-expanded lungs,they're always short of breath,
their blood oxygen level isrelatively well-maintained.
And then the chronic bronchiticare the patients that are not
(05:52):
tall and thin, they tend to beheavier set, they produce a lot
of mucus and they're more proneto having low oxygen levels.
But those two kind ofphenotypes have also fallen out
of favor over the last few years.
There is a dose-responserelationship.
We think that.
(06:15):
Don't quote me on this, butmost people, if they smoke for
less than 20 years, have a verywell 20-pack years that's one
pack a day for 20 years have amuch lower risk of developing
COPD than people who smoke morethan 20-pack years.
One pack a day for 20 years.
Now there are people who arehighly sensitive to the toxins
in cigarette smoke and if theysmoke for five years they can
(06:35):
develop COPD.
So it's not a hard and fastrule.
And one way to gauge kind ofwhere you are in terms of your
lung age is if you're 50 yearsold and you've been smoking for
30 years a pack a day.
You take your 50 years old andyour pack years divided in half,
which would be half of 30, 15.
So you're a 50 year old with a65 year old lung.
(06:57):
That's kind of one easy way tokind of think about it.
Dr. Michael Koren (07:01):
It's interesting Is there any time
after you stop smoking whereyour risk of COPD goes back down
to everybody else's risk?
Announcer (07:08):
Well, the problem with COPD is the C part, the
chronic part.
So once you have COPD your lungfunction is permanently damaged
, and so far we haven't beenable to reverse that, not with
at least the current medicinesthat we've been using for the
last 30 years.
Dr. Michael Koren (07:26):
Okay, all right.
So another audience questionAir pollution can contribute to
the development of COPD True?
False?
I need to listen to theMedEvidence! podcast to know the
correct answer.
Dr. Mitchell Rothstein (07:41):
I think that's three right.
Dr. Michael Koren (07:44):
We should have put one in three as our
actual answer, but yes, true.
Dr. Mitchell Rothste (07:48):
Absolutely .
I think the most obviousexample of this recently is
California and all the wildfiresthey had there.
That's all air pollution.
There's probably been moreparticulate matter and toxins
released into the air inCalifornia in the last three
months since the beginning ofrecorded time, so air pollution
definitely affects thedevelopment of lung damage and
(08:11):
can exacerbate COPD.
Dr. Michael Koren (08:13):
And I think there's a broad way of defining
environmental exposures and airpollution.
Announcer (08:19):
Absolutely so.
Actually, you know what?
The most common cause of COPDin the world is the use of
biomass fuels.
So what's a biomass fuel?
In sub-Saharan Africa, whenthey're cooking, they use animal
dung as their fuel and theycook inside an enclosed area and
(08:42):
they inhale all those fumes.
So that's the leading cause ofCOPD in the world.
Not that many people can affordcigarettes, but they all have
to eat and they all cook theirfood, and that's the biggest
determinant of COPD in the world.
Occupational hazards we knowthat the burn pits that our
soldiers were exposed to inAfghanistan that certainly has
(09:04):
caused COPD in a number of themand any other activity that's
involved with fumes or volatilecarbon odors can all lead to
COPD and damage of your lungs.
You have to remember anythingyou can smell, those molecules
are being filtered by your lung.
(09:26):
So when you smell something bad, those same little molecules
are traveling into your lung andgetting embedded in your lung
tissue and then have to beremoved.
So we're always filteringpollutants out of the
environment in order to keep ourlungs healthy.
Dr. Michael Koren (09:40):
So your take-home advice is that if
you're using dung for cookingpurposes, that you should open a
window.
Dr. Mitchell Rothstein (09:46):
Open a window Well aerated.
Dr. Michael Koren (09:50):
Okay, so talk about genetics.
Dr. Mitchell Rothstein (09:52):
So we do know that there's at least two
genetic diseases that areclearly associated with poor
pulmonary function in the formof this chronic obstructive lung
disease.
One is alpha-1 antitrypsindeficiency.
That's an autosomal recessivegene that's passed on from your
parents.
There are different forms ofthis disease, all worldwide.
(10:18):
There's different alleles thatmake up the alpha-1 antitrypsin
genome.
The ZZ part of the allele isthe most devastating, and what
alpha-antitrypsin does is itreduces the breakdown of lung
tissue.
Trypsin is an enzyme that chewsup lung tissue.
Antitrypsin prevents it fromdoing that.
(10:39):
If you don't produce theantitrypsin, then your lung gets
chewed up.
The other genetic disease iscystic fibrosis.
That clearly causes COPDthrough mucus production and
lung damage.
And then, since the humangenome project was finished, we
know that there's associationswith some other genetic loci
that are associated withincreased risk of COPD
(11:01):
development.
It doesn't mean you'redefinitely going to get them we
don't routinely screen for thembut we know that, like
everything else in this world,there's a bell-shaped curve of
sensitivity to bad things thatcan happen to you, and lung
damage is one of them.
We also know that if your lungshave been damaged from any
(11:21):
reason and in the prebiotic area, we knew that repeated
infections, especially inchildren, can lead to permanent
lung damage.
Basically, your lung reachesits maximum level of function at
about the age of 20 to 25.
Coincidentally, that's whenmost of your elite athletes are
reaching their peak potentialtoo.
(11:42):
And then, after about age 25,we all start to lose function
for the rest of our lives.
Now we lose that function atdifferent rates.
So an average person is goingto die from something other than
loss of lung function at theage of 90.
They'll still have plenty oflung function left, but if that
(12:03):
curve takes a steep downwardtrajectory after being exposed
to infections or constantexposure to pollutants and
cigarette smoke, your curve isgonna be steeper, and you don't
wanna run out of lung functionbefore you run out of life.
Dr. Michael Koren (12:19):
Good way to think about it.
So how about aging?
Announcer (12:23):
Yeah, and this is what I was talking about.
As we get older, we all loselung function.
This may not be that meaningful, but an average person
non-smoking, otherwise healthyloses about 20 cc's of forced
vital capacity lung function ayear and I'll go over that in
just a second.
But that can increase to over100 cc's.
(12:43):
And then in patients that haveCOPD, when they have an
exacerbation of their COPD andrequire hospitalization or other
medicines than their usualmaintenance medicines, they lose
a lot more.
They could lose up to 150 or200 cc's just from that one
episode.
And the thing about COPD isit's not like asthma.
(13:04):
When you get better from COPDyou don't go back to where you
were.
You go back a little bit, butyou're worse than before you had
the exacerbation and I'm goingto talk about this repeatedly.
One of our goals in treatmentnow is to make sure that people
with COPD don't have thoseexacerbations.
Dr. Michael Koren (13:24):
Okay, so to an audience question here.
Which of these is a commonsymptom of COPD Sneezing,
shortness of breath, bad breath,hiccups or a need for an oxygen
tank?
So who says sneezing, who saysshortness of breath, bad breath,
(13:46):
hiccups, need for an oxygentank?
All right, well, I guess thecommon one would be shortness of
breath.
Dr. Mitchell Rothstein (13:54):
That is the common one.
We've got a stacked audienceand nobody's asleep yet.
Nobody's left yet.
and we're more than halfway done.
So we're going to get there.
So the shortness of breath.
You know, when people come tosee a cardiologist or a
pulmonologist, one of the mostcommon complaints we get always
is that they're short of breath.
So when they come to see Dr.
(14:14):
Koren, he says, well, it's notyour heart, it must be your
lungs.
And when they come to see me, Isay, well, it's not your lungs,
it must be your heart.
And so what we want to do isfigure out which one it really
is.
And how does lung disease makeyou short of breath?
And that is the most commoncomplaint.
And if you're seeing apulmonary specialist, he's
probably giving you a littlequestionnaire called an MMRC,
(14:36):
which is a kind of like the NewYork heart classification.
It says I get short of breathwhen I'm doing daily activities,
when I make the bed, when Iwalk one flight of stairs, and
it helps us kind of gauge thedisability of the patient based
on their answer to that and thelevel of their lung function.
Dr. Michael Koren (14:54):
Yeah, and a couple of people raised their
hand for an oxygen tank, but Ithink it's fair to say that the
people that need to walk aroundwith an oxygen tank are a very
small percentage of all peoplewith COPD.
Dr. Mitchell Rothste (15:03):
Absolutely ,
is that fair to say?
Dr. Mitchell Rothstein (15:05):
Yeah.
So it's when people requireoxygen therapy and I'm going to
show you why they do that injust a second but that means
that their lung function hasreally deteriorated quite a bit
and that you're clearly at apoint where you have to be
careful about everything.
Dr. Michael Koren (15:20):
And that's maybe one or two percent of all
people with COPD.
Dr. Mitchell Rothstein (15:23):
Yeah, less than 5%.
Dr. Michael Koren (15:25):
Okay.
Okay, how about cough?
We talked last month aboutcough and, excuse me, we're
doing speaking of cough, butwe're doing some research right
now, because cough is a verycommon symptom.
You and I were just talkingabout how many coughs is normal
versus how many coughs a day isabnormal.
(15:46):
It's one of those things thatonly crazy, nerdy people like us
think about, but it's importantbecause this can be disabling
for some folks Absolutely, andthere's a lot of reasons people
get cough, but is COPD one ofthem.
Announcer (15:59):
Absolutely so.
Part of COPD is chronicinflammation.
With that chronic inflammationyou have chronic mucus
production and that mucus endsup in your airways.
Those airways are innervated bynerves that are connected to
your brain that induce thatcough reflex.
Additionally in your lungs youhave something else, receptors
(16:20):
that are called J-receptors orstretch receptors, and people
that have COPD and have damaged,over-inflated lungs, those
J-receptors are activated alsoand they cause that cough urge.
So not everybody.
You don't have to choke on achicken sandwich to cough.
You can cough, because there'sthings going on in your lung
tissue chronically all the timethat are activating those nerves
(16:41):
.
Dr. Michael Koren (16:42):
And so Dr.
Rothstein and I were talkingabout the fact that there are a
lot of people out there thatcough more than 15 times an hour
, and it's not clear why they dothat.
Right, they cough less whenthey're sleeping, of course, but
when they're awake you mayclear your throat a little bit,
just like a little cough or justa more prominent cough, and if
you have that issue, there's aphone number you can give us a
(17:04):
call.
We can get you involved in someof the research, and this is
the benefit to the patients isthat we'll actually put a
monitor on you to see howfrequently you cough.
So one of the crazy things thatwe do in research is really
analyze the type of problemspeople have, and you may or may
not get in the study, but you'llget the information about your
cough frequency.
Dr. Mitchell Rothste (17:22):
Absolutely .
It's a fascinating study andit's the first study that's
looking at a drug indicated forthis specific indication.
So there's no medicine outthere now that's approved for
chronic cough.
You know we give peoplenarcotics to slow down their
cough, benzonatate to slow downtheir cough.
None of those have been reallyproven to work effectively.
(17:43):
And this is attacking this kindof neurogenic reflex that we
know is active in people, andwe're not including copd
patients in the study right now.
First we want to see if it workson people that don't have
intrinsic problems with theirlungs
Dr. Michael Koren (17:57):
But the nice part of the research process, of
course, is we'll help you sortit out right while you have, why
you may be having that orsomebody you know may have that.
All right, so let's talk aboutthe grim signals now of COPD.
Dr. Mitchell Rothstein (18:09):
So you know, and when we look at
patients with COPD we kind oftry to match the treatment to
their symptoms, not so muchtheir numbers.
The numbers, these breathingtests we use in COPD, are
basically to make a diagnosisand then, based on symptoms, is
how we treat people.
And the symptoms that we'reprimarily looking at are listed
(18:30):
here.
It's fatigue, it's shortness ofbreath, it's increased
shortness of breath withactivity, it's wheezing and
mucus production, chesttightness and, like I said about
COPD, it's a chronic diseaseand over time it's going to get
worse.
How quickly it gets worse, youknow, nobody knows until we're
following people over time it'sgoing to get worse and can
(18:52):
measure their symptoms and theirbreathing tests and see what
kind of trajectory on.
But we know that if you'resymptomatic from COPD now left
alone, it's not going to getbetter on its own.
Dr. Michael Koren (19:07):
So give us a little bit more insight into
exactly what your lungs do on aday-to-day basis.
Dr. Mitchell Rothstein (19:11):
Yeah, Well, this is important for me
because I always have to remindmyself and it's always, I think,
difficult for people that haveCOPD or don't have COPD as to
what our lungs actually do.
So your lungs have twooperational details.
Number one is to ventilate, soit moves air in and out of your
(19:32):
lungs and it does it throughthese airways.
So you can see the mainwindpipe there, your trachea,
and then it divides in half intoyour we call main stem bronchi,
and then those airways divide23 more times until it reaches
the end, aviolus, where theperfusion part starts.
(19:52):
And if you line up all thoseairways, that's 1500 miles of
airway that we each have in ourlungs.
So you can imagine if you havesome mucus in all 1500 miles,
it's going to increase the workof getting air past all that
mucus.
And the other thing that happensis only in the main windpipe
(20:13):
and those bronchi that come tothe top are the airways
supported by cartilage.
After that main division, theairways are just muscular tubes,
so they're like blood vesselsalmost.
They can be easily compressed.
If you breathe in real fast orbreathe out real fast, they
expand and collapse and that cancause problems with the air
(20:34):
movement too.
So the other thing that yourlung does is this perfusion and
if you go to the next slide,
there's one other thing you'releaving out.
There are two nice pillows, sothat the heart is comfortable in
the middle.
Well as a lung specialist you know I
know the heart only has onepurpose and that's to pump blood
to the lungs.
So as a cardiologist Dr.
(20:55):
Koren has a differentperspective on it I see it as
taking up valuable lung room.
So then, once you get down toall those airways, what they end
in is something called thealveolus, which you see here,
and these are tiny little bubblesacks and every alveolus has a
blood vessel that you can see inthis diagram here, that kind of
(21:17):
wraps around it, and there areabout three or four million of
these little bubble sacks ineach lung and if you spread all
those out it'd be 75 squaremeters of bubble sacks, a tennis
court of bubble sacks that allthese blood vessels wrap around.
And the blood that starts tocome in and wraps around the
(21:38):
lung doesn't have any oxygen,has lower oxygen levels in it
and high carbon dioxide levels,because that's all your body is
Metabolizing.
So now the bloods taking thisextra carbon dioxide and lower
oxygen level to your lungs forthe perfusion.
Part of this now Interestinglyand I'll be real quick with this
carbon dioxide is a much morediffusible gas than oxygen is.
(22:01):
So from the time that Bloodhits that alveolus, the carbon
dioxide comes out very quicklyand about the first 15% of that
transit time around the alveolusthe oxygen takes longer about
75% of the transit time to getall the oxygen into the blood.
So in the alveolus you've gotthe carbon dioxide coming out of
(22:23):
the blood, the oxygen from thealveolus going into the blood,
and then you blow it out.
So every minute you'rebreathing in and out about six
liters of air and every minuteyou're pumping about five liters
of blood.
And there's a little overlap onthe lung side because we know
the heart's not that efficient,so you have to kind of make up
(22:44):
for that problem
Dr. Michael Koren (22:48):
the anti-cardiac Society will be
calling you.
You'll be getting a letter fromour attorney.
Dr. Mitchell Rothstein (22:53):
So the importance of this is this is
where the gas exchange occurs,so you can see if you're
damaging this, if these bloodvessels are getting squeezed off
or if the alveolus is gettingdestroyed the carbon dioxide.
Usually there's enough roomleft for the carbon dioxide to
get out, but the oxygen doesn'talways have time to get in and
(23:14):
then people need to be onsupplemental oxygen.
If you've lost your ability toget rid of carbon dioxide and
that level's going up in yourbloodstream, we call that
hypercapnic respiratory failure.
That's a much more seriousadvanced condition.
Dr. Michael Koren (23:30):
All right.
So another audience questionhere which of the following is a
test that doctors use todiagnose COPD?
One spirometry, twoplethysmography.
Three pulse oximetry.
Four tomography or five, all ofthe above.
Dr. Mitchell Rothstein (23:50):
Yeah well, spirometry is the test
that we use to diagnose COPD.
We do pulmonary function teststhat include a lot of this other
stuff.
I don't have time to explainbecause Dr.
Koren took up a long time.
That's fine, so we'll go aheadwith spirometry.
Dr. Michael Koren (24:04):
I'll give you two minutes but explain that a
little bit more, because peoplethought it was all the above,
but when you really look at thequestion in terms of the formal
diagnosis of COPD, it's a littlebit different.
So go ahead.
Dr. Mitchell Rothstein (24:17):
So spirometry we're going to show
you a slide about.
Plethysmography is ameasurement that we use to look
at lung volume.
So we have different volumesthat we associate with our lungs
.
So when I take in a deep breathfrom resting, so I have a
normal exhalation and then Itake a deep breath in from that
point, that's my inspiratorycapacity.
(24:39):
That's one volume.
If I blow all the air out of mylungs until no more air can
come out, that's my vitalcapacity.
But even at the end of thatthere's still some air left in
my lungs and that's called theexpiratory reserve volume.
And then looking at differentvariations on how that air comes
(25:00):
out is part of the spirometricanalysis that we use to diagnose
COPD.
Pulse oximetry measures youroxygen level in your bloodstream
.
It's got a little bit of errorinvolved in it.
For a normal person at sealevel it's about 94% plus or
minus 2%.
As you go up and there's lessoxygen, that number obviously
(25:23):
comes down.
Tomography we don't use so muchin breathing tests or in lung
evaluation.
So it's really the first threethat are associated with lung
testing and spirometry is themost important for diagnosing
obstructive lung disease and whydon't we go on to the next one?
So, obstructive lung disease,there's really two types.
(25:45):
There is COPD, and then there'sasthma, and then there's this
condition called an overlapsyndrome that has a lot of
characteristics of both, butspecifically with COPD, we
measure the total amount of airthat I can blow out from one
deep inhalation.
I blow the air out as fast as Ican and then at six seconds, if
(26:08):
I last that long, that totalamount of air that comes out is
called the forced vital capacity.
Of that, the part that comesout, why don't we go to the next
slide?
And I can show them better.
So of that, if you look at thistop curve, the lines going up
right, right and I'm blowing airout, that's the forced vital
capacity.
If you look at the amount ofall that air that comes out the
(26:32):
amount that came out in thefirst second, and you can see
that most of it, about 80% orbetter, is coming out very
quickly, right at the beginning.
Dr. Michael Koren (26:41):
This is a second, I take it right?
Dr. Mitchell Rothstein (26:43):
Right Time in seconds on the bottom,
right, right, and so as that,all that air that comes out,
most of it comes out veryquickly at the beginning.
So when we do this spirometrytest we look at your spirometry
and we say how much of all theair that came out came out in
the first second and if it'sless than 70% that's called
(27:04):
obstructive lung disease.
And when it's less, that curveon the top, mike kind of
flattens and doesn't rise up asquickly as it did on the normal
patient.
Now the exception to this is ifyou have obstructive lung
disease, meaning that FEV1 wasless than 70% of the total, and
then we give you like an inhalerand it goes to better than 70%,
(27:27):
you have asthma, you don't haveCOPD.
So this is the test that tellsus in large groups of people
whether or not they have COPD.
So an FEV1 less than 70%.
And the nice part about this isyou're your own control.
You know we're not comparingyour test to a lot of other
people's tests.
For this FEV1 percent test it'syour total versus the amount
(27:51):
that came out in the firstsecond and if that's reduced too
low then you have COPD.
If it doesn't improve.
Dr. Michael Koren (27:56):
So, to paraphrase what you just said,
just and connect it with thepicture so if this is what your
spirometry looks like, you usean inhaler and then it starts
looking like that
Dr. Mitchell Rothstein (28:06):
Correct.
Dr. Michael Koren (28:06):
Then that's asthma, not COPD,
Dr. Mitchell Rothstein (28:08):
Correct.
Announcer (28:08):
If it returns to normal.
Dr. Michael Koren (28:10):
Thank you.
Dr. Mitchell Rothstein (28:12):
So these are kind of the after effects
of what COPD does on a chestx-ray.
So this is a normal chest x-rayon your left and you can see
the heart silhouette.
The patient is looking out atyou, right shoulder, left
shoulder, and you can see theheart silhouettes there.
There are where that green andpurple arrows are are the blood
vessels in the heart, in thelungs.
(28:34):
You can barely see them, andthen these curved things on the
bottom are your diaphragms.
So when we breathe in, webreathe in under negative
pressure, we suck air in.
So when we breathe in, weexpand our diaphragm so they
contract and they go down.
That creates negative pressurein our chest and we suck the air
in.
Now, when patients develop COPD,they have this obstructive
(28:56):
problem to airflow and they getthe air never fully exhaled and
they keep hyperinflating.
They keep getting more and moreair stuck in their chest and it
leads to an x-ray that lookslike that.
So you can see where thediaphragm should have been,
where those lines are and wherethey are now.
You can also see the bloodvessels that are going into the
(29:18):
lungs now are very prominentbecause the lung tissue has been
destroyed and the heart ishaving a difficult time pumping
all that blood to the lungsagain.
So those blood vessels tend todevelop to increased pressure.
So you can experience thisright now at your table If you
take a breath in and then try totake another breath on top of
(29:41):
that.
That's how that person feels allthe time.
Every breath is a consciouseffort.
They're short of breath all thetime time.
They don't have that room fortheir diaphragms to contract
anymore and go down.
So the differences between COPD.
In general we know that both ofthem can have swollen, narrow
(30:01):
airways.
We know that in asthma, like wewere saying, if you use that
inhaler and the breathing testgoes back to normal, we call
that reversibility.
That happens much more often inasthma.
Patients with COPD may have aresponse to bronchodilators but
they never go back to normal orelse we'd call them asthmatics.
We know that people with asthma, their symptoms can come and go
(30:22):
, they can have flares of asthma.
With COPD that sense ofshortness of breath tends to be
more constant.
In asthma because their airflowcan go back to normal.
We know that that's true.
In COPD, it never goes back tonormal.
Asthmatics tend to have ayounger age of onset than people
with COPD, who typicallydevelop the disease in their 40s
(30:42):
, 50s and upward.
But you can develop asthma atany age as well, and we know
that the allergic background ismuch more prominent in
asthmatics than it is in COPDpatients.
But we're learning that thereis some type of this type 2
inflammatory allergic responsein COPD patients that may have
more significance than wethought.
(31:06):
So the goals of treatment withCOPD are we can't cure it.
We want to slow down theprogression and we want to
improve patients' abilities toengage in activities of daily
living.
And the key to COPD control isreducing these exacerbations,
(31:27):
because if we can reduce thosebig drops in lung function, we
think that will improve qualityof life.
So how do we do that right now?
So when I was in training, mostof the things I'm going to talk
about weren't even in the realmof treatment options.
But now we know the best thingyou can do is stop smoking.
(31:50):
That's going to help reducethat fall in your lung function
and reduce cardiovasculardisease and everything else that
goes along with it.
We have the slew of medicinesthat we use in COPD Pulmonary
rehab, this exercise programthat anybody with symptomatic
COPD should go through.
So symptomatic means if youhave COPD and you're short of
(32:13):
breath, even if you haven't beenhospitalized, you want to go
through a pulmonary rehabprogram.
We know that that improvesquality rehab program.
We know that that improvesquality of life.
We know it reducesexacerbations and we know it
reduces hospitalizations andshort term it has a reduction on
mortality as well.
Supplemental oxygen if neededand like Dr.
Koren was saying, it's lessthan about one.
(32:35):
Two percent of our patientswith COPD need supplemental
oxygen.
But if you need it it isassociated with increased
quality of life and increasedlife expectancy.
We've developed non-invasiveventilation which is kind of
like you know a CPAP.
You know CPAP for patients withsleep apnea.
Well, we have a CPAP that cankind of act like a ventilator to
(32:58):
help people breathe at night.
That can reduce that work ofbreathing so people can sleep
through the night if their COPDis that progressive.
We have also been doingsurgeries on lungs.
You've probably heard of lungvolume reduction surgery.
So if people have emphysema,these big blebs in their lungs,
we know that we can take thebleb out and that allows normal
(33:22):
lung that's left over tore-expand and to function more
normally and that can improvetheir sense of dyspnea and
quality of life Without doingsurgery.
In one of those tiny littleairways we can put a one-way
valve that kind of shuts theblood flow and the oxygen off to
that part of the lung and thatlung will collapse, essentially
(33:42):
doing an autobulectomy.
The rest of the lung willexpand and improve quality of
life and send some dyspnea there.
And then we've also done lungtransplantation in patients with
primarily unilateral diseaseand primarily of an
emphysematous type, but that'salso been one of the surgical
approaches as well.
Dr. Michael Koren (34:02):
I haven't heard as much lately about
volume reduction surgeries as Idid 20 years ago.
Is that falling out of favor alittle bit?
Announcer (34:08):
It's falling out of favor because of the
endobronchial valves.
Instead of, you know, crackingyour chest open, we can down in
the bronchoscopy suite, put thatvalve in and get almost the
same result.
Dr. Michael Koren (34:18):
Got it.
Dr. Mitchell Rothstein (34:23):
And then there's clinical trials.
So, and then the clinical trialsthat are going on are
addressing Medications that willimprove lung function, delivery
of those medicines to improvelung function, as well as a
(34:43):
bunch of anti-inflammatorymolecules that have just come
out in the last decade that arehaving surprising results in
COPD patients in terms ofhelping them improve lung
function, reducehospitalizations and reduce
exacerbations.
So the old traditionalmedications that we used in COPD
are basically divided up intothree groups.
We have the beta agonist, whichis like albuterol that we use
(35:07):
in asthma.
They tend to be short.
There's one group that tends tobe short-acting that lasts a
couple, three hours, and thenlong-acting that can last 12 to
24 hours, and these medicineswork by increasing this mediator
called cyclic AMP in the musclecell, which causes these muscle
(35:27):
tubes to relax and they getbigger, and it's been very
effective and has a relativelyshort onset of action.
We call them rescue medicines.
When it's the short-actingvariety, it can give people
relief within minutes.
And then the next major classis these go to the next slide.
(35:47):
Are these anticholinergic agents, or we call them LAMAs,
anti-muscarinic agents, andthey're largely used in patients
with COPD.
Ipitropium is one that's beenout for about 20 years.
It's now finding a place in theuse and treatment for asthma as
well.
And instead of activelydilating the airways, what these
(36:11):
anticholinergic medications dois they interfere with the
ability of the airways toconstrict, so they relax them,
but they don't actively relaxthem.
They're very effective.
Also, they come as ashort-acting medication and a
long-acting, a LAMA medicationas well, and there's a bunch of
different names for thedifferent products there.
(36:31):
I won't go through them becauseMike used up all my time.
Go on to the next slide andthen we have this group of
medicines called inhaledcorticosteroids.
So when I did my training backin the well, whenever, the first
use of inhaled corticosteroids-
Dr. Michael Koren (36:49):
Which century was that?
Dr. Mitchell Rothstein (36:53):
-so it just coming out onto the
marketplace and it was used.
We were using it in patientswith asthma the marketplace and
we were using it in patientswith asthma and all of a sudden,
instead of having an ICU fullof asthma patients on
ventilators and with a very highdeath rate, nobody was showing
up to the ICU anymore becausethese inhaled corticosteroids
(37:13):
were great at reducing theinflammation in the airways in
these asthmatic patients and itreduced those exacerbations and
the need for them to seekhospitalization.
So we translated that success inasthma patients to patients
with COPD and I think you'veseen widely advertised on TV and
(37:36):
probably some of you may beeven using them.
We kind of combined all thesegroups of medicines together and
now kind of standard therapy wecall it triple therapy for
patients with COPD is along-acting beta agonist, that
one that actively dilates theblood vessels, a long-acting
muscarinic agent, which is onethat prevents the airways from
(37:59):
constricting, and an inhaledcorticosteroid.
And those can be very expensiveand we're not sure if it's
really beneficial in all COPDpatients.
One of the interesting thingsthey found that when they looked
at patients with COPD thepatients that used inhaled
corticosteroids had decreasedacute myocardial events over a
(38:19):
decade but, they had increasedrisks of pneumonia and upper
respiratory tract infections.
So we're trying to sort that out.
So inflammatory versuspro-infection.
Dr. Mitchell Rothste (38:30):
Absolutely
Dr. Michael Koren (38:31):
Interesting.
Dr. Mitchell Rothstein (38:34):
So these are the different kind of
combinations SABA is ashort-acting beta agonist used
with a LABA, a long-acting betaagonist, and a LAMA, a
long-acting muscarinic agent.
And then you can use the tripletherapy the LABA, LAMA, and ICS
.
Now these are all given byinhalation and one of the
(38:55):
problems with COPD is you can'treally breathe that well to
begin with.
So part of the problem with ourtherapy is if you can't actuate
the device or open the deviceand inhale deep enough to get
the medicine to your lungs, itdoesn't work as well if you just
go and the medicine just goesinto the back of your throat.
(39:17):
So we have a bunch of goodmedicines for people, but a lot
of people have difficulty usingthem and I can tell you in my
practice, every time I saw apatient for follow-up that was
using inhalers, I asked them touse it in front of me just to
make sure they were doing itadequately, and 50% of the time
people would have their actuatorand they'd show me up, they'd
(39:38):
squeeze it.
It didn't even go in theirmouth and then they'd inhale and
you'd say, well, we went overthis, you know, three months ago
, and it takes a lot ofrepetition if you're not doing
it every day, it's a hard skillto kind of master.
So over the last 15 years we'verealized that there's other
inflammatory components to COPDand not just treating the airway
(40:01):
, opening and closing.
Among those are these a bunchof inflammatory cytokines and
alarmants.
They have a huge number ofdifferent names and it's just
more and more.
The more I read on this, themore confused I get as to which
pathway what's interfering with,the more confused I get as to
which pathway what's interferingwith.
Daliresp or roflumilast came outas a phosphodiesterase
(40:23):
inhibitor type 4.
So we have about six of thesephosphodiesterase inhibitor
types.
Two of them are pertinent toyour lungs, four is the most
common, but there's also three.
And what phosphodiesterase doesis it inhibits the breakdown of
cyclic AMP, which causes theblood vessels, the airways, to
(40:45):
dilate.
So these medicines reduceinflammation in the airways and
they cause them to dilate alittle bit.
More, recently Ensifentrine,came out and that's a PDE3 and 4
inhibitor and it seems to bemuch more potent than Daliresp
has been and that seems to notonly improve lung function but
(41:08):
also reduce exacerbations andhospitalizations.
And Ensifentrine and Dupilumab,which is a monoclonal antibody.
You've probably it's calledDupixent.
You've probably seen itadvertised for eczema and for
asthma.
We now know that that medicineis also effective in COPD
patients.
(41:28):
But there's a certain type ofCOPD patient that that's
important for, and that'spatients that on their blood
counts have high eosinophiliclevels.
Like I said before, the allergyis more common in asthma than
it is in COPD, but we know thatthere's patients with COPD that
have that allergic component andthey seem to respond to this
(41:48):
quite nicely.
Dr. Michael Koren (41:50):
Yeah, I think you told me this anecdote about
how important it is to actuallywatch patients use the inhalers
.
I think you told me about thisanecdote where you asked
somebody to do that.
The person sprayed it in theair and then put their face in
the mist.
So it's more than a trivialpoint.
Dr. Mitchell Rothstein (42:08):
I would say that in my practice and I
practiced for over 30 years thatmy patients with COPD, one that
actuated and inhaled properlywas about 50%, and then of the
people that did that properly,the people that could get a deep
enough inhalation in to reallymaximally benefit from the
medicine, was about 75%.
(42:30):
So a lot of these medicineslose their power Now.
Interestingly, some of thesemedicines are now available by
nebulizer and we're going tohave a study, hopefully in the
next few months, that is, usinga nebulizer just twice a day,
using these long-acting products, so that people will actually
get a benefit from theirmedicine.
Dr. Michael Koren (42:48):
That's interesting, yeah.
Dr. Mitchell Rothstein (42:49):
So among the biologics, Dupixent isn't
the only monoclonal antibody outthere that's looking
specifically for these eithereosinophilic type or
non-eosinophilic type COPDpatients.
There's a list here of theothers, some of their target
compounds, and they're kind ofgoing through this trying to
find out which medicine is rightfor what we call them phenotype
(43:12):
, either an eosinophilic or anon-eosinophilic dominant
patient with COPD, and at leastwith the eosinophilic group we
know that the depiction ishaving a marvelous effect on
helping them reduceexacerbations.
Dr. Michael Koren (43:26):
Yeah, and if you want to impress your friends
at a cocktail party, you'llnotice that all the monoclonal
antibodies end with MAB.
So if somebody has aninjectable drug they're using
and you can tell them if it's amonoclonal antibody or not just
by looking at it.
Okay, well, now somethingimportant.
Yeah, COPD in thecardiovascular system Go ahead.
Dr. Mitchell Rothstein (43:46):
Patients that have COPD you know it's
the people that smoke a lot tendto run the risk of heart
disease.
So we know that.
You know we're dealing withpatients that often have two
comorbidities they have lungdisease and they have heart
disease.
We know that if you have anexacerbation of COPD, you're
going to be at risk for havingan acute myocardial or
(44:07):
cardiovascular event as wellstroke or heart attack and that
as COPD progressed, when thoselittle bubble sacks, alveoli get
destroyed and the blood supplygets destroyed and the heart is
still pumping that five litersper minute through the heart,
but it's a smaller vascular bedthose blood vessels are under
increased pressure and thatleads to pulmonary hypertension,
(44:30):
which then causes moreshortness of breath.
An interesting fact, too, isthat if you lose 10% of your
forced vital capacity, your riskof having an acute myocardial
event increases by 10%.
Dr. Michael Koren (44:42):
Interesting I had not heard that statistic.
Dr. Mitchell Rothstein (44:45):
Yeah, so pulmonary rehab, like I said,
should be a mainstay withanybody with a symptomatic COPD.
It's a supervised classroomexperience.
It teaches people how to dothings without putting their
respiratory system underincreased stress, as well as
increasing their stamina, and weknow that it improves quality
of life, reduces breathlessness,reduces exacerbation and
(45:08):
hospitalization rates.
Announcer (45:09):
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