Announcer:
0:00
Welcome to the MedEvidence! podcast. This episode is a rebroadcast from a live MedEvidence! presentation.
Dr. Michael Koren:
0:06
I'm really excited to learn about COPD chronic obstructive pulmonary disease and you've been spending your whole career as an expert on this and I don't know anybody more knowledgeable, so let's run through it. Let's educate everybody about COPD.
Dr. Mitchell Rothstein:
0:22
And just before I get started, Dr Koren was very concerned that I had too many slides and I was going to take too long. So he took up the first five minutes of my time and I said, well, I'll push through it. So my goal is to still push through it, not have any of you fall asleep, despite your tendency and not to have anybody leave,
Dr. Michael Koren:
0:39
so that's where you learn the truth. I'm a time hog.
Dr. Michael Koren:
0:44
So go for it, Mitch.
Dr. Mitchell Rothstein:
0:50
All right. So when we talk about COPD, what does it stand for? So chronic obstructive pulmonary disease? Chronic means it's there all the time, doesn't go away. It may get better, maybe get a little worse. Obstructive means that there's airflow obstruction. I'll go into that in just a second Pulmonary. It's affecting the lung tissue and disease that there's damage to that organ. So why don't you take this one?
Dr. Michael Koren:
1:09
Yeah, so we always like to have input from the audience and we always like to say that there's no free lunch. You have to work for it. So, with that in mind, which of the following statements is true about COPD? Most cases of COPD are caused by inhaling pollutants, Fumes, chemicals and dust found in many work environments are contributing factors. Genetics can play a role if an individual's development of COPD, even if the person has never smoked or all of the above, Okay.
Dr. Michael Koren:
1:39
You see, we have a really smart audience here, right, so we can just skip to the end. There we go, okay.
Dr. Mitchell Rothstein:
1:44
And here, which of the following is false? This is one of those SAT questions. You have to read it carefully. Which is false? Most people with COPD have not been diagnosed. COPD patients may have had a history of asthma. Most COPD patients do not have breathing tests that prove that they have COPD patients do not have breathing tests that prove that they have COPD. Copd patients should not receive vaccines for RSV, covid or flu, or most COPD patients die from heart disease. So one of these is false, who thinks one is false, who thinks two is false, who thinks three is false, who thinks four is false and who thinks five is false?
Dr. Mitchell Rothstein:
2:27
All right, well this is pretty good, you guys. So obviously Did you sell the answers to this test beforehand.
Announcer:
2:34
Well, it's obviously an educated group. I mean, they knew they were coming for a COPD talk.
Dr. Michael Koren:
2:37
There we go. They were prepared.
Dr. Mitchell Rothstein:
2:39
Yes, it's a subselect group.
Announcer:
2:41
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 development of COPD from when people actually stop smoking or have inhalational injuries. So we're still starting to see that tsunami from the 70s and 80s when people really started to stop. We know it's progressive. It affects more than 14 million people in the United States that we have diagnosed. We think there's probably at least twice as many that have COPD that are undiagnosed. It's chronic inflammation of the airways and the lung tissue results in reduction in airflow, which makes it then difficult to breathe. That work of breathing has increased and we've realized over the last 20 years that there's really two different kind of phenotypes of COPD. There's a phenotype that has just inflammatory cells in their lungs and then there's a phenotype that has inflammatory cells and eosinophils like an asthma component in their lungs. So this is an interesting part.
Dr. Mitchell Rothstein:
3:47
Yeah, you showed this to me earlier today. This is fascinating.
Dr. Mitchell Rothstein:
3:51
So this is NIH funding from 2015 for different diseases and then the deaths per year from those diseases. So the NIH funded Parkinson's disease to the tune of 146 million. There were 28,000 deaths. Alzheimer's disease got 589 million for 110,000 deaths. Liver disease got 616 million for 50,000 deaths. And HIV got $3 billion for 6,500 deaths. And COPD was funded 37 million, far below any of these others, and there were 150,000 deaths in those years.
Dr. Michael Koren:
4:29
Right, and so a lot of this is probably driven by politics is you have advocacy groups that go out and get the government to spend money in their disease of concern.
Dr. Mitchell Rothstein:
4:40
And as well as there's a little kind of a social aspect to it too. People that smoke get COPD largely and there's kind of this is a self-induced disease and people are less happy about funding those quote types of diseases.
Dr. Michael Koren:
4:55
Yeah, people who smoke can make the argument that they're paying a lot of taxes every time they buy cigarettes and their tax money should go to use to figure out what to do about it.
Dr. Michael Koren:
5:04
And the government was instrumental in getting them addicted to nicotine.
Dr. Michael Koren:
5:06
There we go,
Dr. Michael Koren:
5:09
all right.
Announcer:
5:10
So, speaking of smoking, we know that cigarette smoking in the United States the leading cause of COPD. There's 5,000 chemicals in cigarette smoke, including formaldehyde and benzene that you're inhaling into your lungs and all these cause inflammation and destruction of the lung tissue, as well as inflammation, mucus production in the airways, leading to these two kind of phenotypes of COPD. One is called an emphysematous patient and those are patients we used to call them pink puffers. They have hyper-expanded lungs, they're always short of breath, their blood oxygen level is relatively well-maintained. And then the chronic bronchitic are the patients that are not tall and thin, they tend to be heavier set, they produce a lot of mucus and they're more prone to having low oxygen levels. But those two kind of phenotypes have also fallen out of favor over the last few years.
Announcer:
6:07
There is a dose-response relationship. We think that. Don't quote me on this, but most people, if they smoke for less than 20 years, have a very well 20-pack years that's one pack a day for 20 years have a much lower risk of developing COPD than people who smoke more than 20-pack years. One pack a day for 20 years. Now there are people who are highly sensitive to the toxins in cigarette smoke and if they smoke for five years they can develop COPD. So it's not a hard and fast rule. And one way to gauge kind of where you are in terms of your lung age is if you're 50 years old and you've been smoking for 30 years a pack a day. You take your 50 years old and your pack years divided in half, which would be half of 30, 15. So you're a 50 year old with a 65 year old lung. That's kind of one easy way to kind of think about it.
Dr. Michael Koren:
7:01
It's interesting Is there any time after you stop smoking where your risk of COPD goes back down to everybody else's risk?
Announcer:
7:08
Well, the problem with COPD is the C part, the chronic part. So once you have COPD your lung function is permanently damaged, and so far we haven't been able to reverse that, not with at least the current medicines that we've been using for the last 30 years.
Dr. Michael Koren:
7:26
Okay, all right. So another audience question Air pollution can contribute to the development of COPD True? False? I need to listen to the MedEvidence! podcast to know the correct answer.
Dr. Mitchell Rothstein:
7:41
I think that's three right.
Dr. Michael Koren:
7:44
We should have put one in three as our actual answer, but yes, true.
Dr. Mitchell Rothstein:
7:48
Absolutely. I think the most obvious example of this recently is California and all the wildfires they had there. That's all air pollution. There's probably been more particulate matter and toxins released into the air in California in the last three months since the beginning of recorded time, so air pollution definitely affects the development of lung damage and can exacerbate COPD.
Dr. Michael Koren:
8:13
And I think there's a broad way of defining environmental exposures and air pollution.
Announcer:
8:19
Absolutely so. Actually, you know what? The most common cause of COPD in the world is the use of biomass fuels. So what's a biomass fuel? In sub-Saharan Africa, when they're cooking, they use animal dung as their fuel and they cook inside an enclosed area and they inhale all those fumes. So that's the leading cause of COPD in the world. Not that many people can afford cigarettes, but they all have to eat and they all cook their food, and that's the biggest determinant of COPD in the world.
Announcer:
8:57
Occupational hazards we know that the burn pits that our soldiers were exposed to in Afghanistan that certainly has caused COPD in a number of them and any other activity that's involved with fumes or volatile carbon odors can all lead to COPD and damage of your lungs. You have to remember anything you can smell, those molecules are being filtered by your lung. So when you smell something bad, those same little molecules are traveling into your lung and getting embedded in your lung tissue and then have to be removed. So we're always filtering pollutants out of the environment in order to keep our lungs healthy.
Dr. Michael Koren:
9:40
So your take-home advice is that if you're using dung for cooking purposes, that you should open a window.
Dr. Mitchell Rothstein:
9:46
Open a window Well aerated.
Dr. Michael Koren:
9:50
Okay, so talk about genetics.
Dr. Mitchell Rothstein:
9:52
So we do know that there's at least two genetic diseases that are clearly associated with poor pulmonary function in the form of this chronic obstructive lung disease. One is alpha-1 antitrypsin deficiency. That's an autosomal recessive gene that's passed on from your parents. There are different forms of this disease, all worldwide. There's different alleles that make up the alpha-1 antitrypsin genome. The ZZ part of the allele is the most devastating, and what alpha-antitrypsin does is it reduces the breakdown of lung tissue. Trypsin is an enzyme that chews up lung tissue. Antitrypsin prevents it from doing that. If you don't produce the antitrypsin, then your lung gets chewed up. The other genetic disease is cystic fibrosis. That clearly causes COPD through mucus production and lung damage. And then, since the human genome project was finished, we know that there's associations with some other genetic loci that are associated with increased risk of COPD development.
Dr. Mitchell Rothstein:
11:01
It doesn't mean you're definitely going to get them we don't routinely screen for them but we know that, like everything else in this world, there's a bell-shaped curve of sensitivity to bad things that can happen to you, and lung damage is one of them.
Dr. Mitchell Rothstein:
11:18
We also know that if your lungs have been damaged from any reason and in the prebiotic area, we knew that repeated infections, especially in children, can lead to permanent lung damage. Basically, your lung reaches its maximum level of function at about the age of 20 to 25. Coincidentally, that's when most of your elite athletes are reaching their peak potential too. And then, after about age 25, we all start to lose function for the rest of our lives. Now we lose that function at different rates. So an average person is going to die from something other than loss of lung function at the age of 90. They'll still have plenty of lung function left, but if that curve takes a steep downward trajectory after being exposed to infections or constant exposure to pollutants and cigarette smoke, your curve is gonna be steeper, and you don't wanna run out of lung function before 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 lose lung function. This may not be that meaningful, but an average person non-smoking, otherwise healthy loses about 20 cc's of forced vital capacity lung function a year and I'll go over that in just a second. But that can increase to over 100 cc's. And then in patients that have COPD, when they have an exacerbation of their COPD and require hospitalization or other medicines than their usual maintenance medicines, they lose a lot more. They could lose up to 150 or 200 cc's just from that one episode. And the thing about COPD is it's not like asthma. When you get better from COPD you don't go back to where you were. You go back a little bit, but you're worse than before you had the exacerbation and I'm going to talk about this repeatedly. One of our goals in treatment now is to make sure that people with COPD don't have those exacerbations.
Dr. Michael Koren:
13:24
Okay, so to an audience question here. Which of these is a common symptom of COPD Sneezing, shortness of breath, bad breath, hiccups or a need for an oxygen tank? So who says sneezing, who says shortness of breath, bad breath, hiccups, need for an oxygen tank? All right, well, I guess the common one would be shortness of breath.
Dr. Mitchell Rothstein:
13:54
That is the common one. We've got a stacked audience and nobody's asleep yet. Nobody's left yet.
Dr. Mitchell Rothstein:
13:59
and we're more than halfway done.
Dr. Mitchell Rothstein:
14:01
So we're going to get there. So the shortness of breath. You know, when people come to see a cardiologist or a pulmonologist, one of the most common complaints we get always is that they're short of breath. So when they come to see Dr. Koren, he says, well, it's not your heart, it must be your lungs. And when they come to see me, I say, well, it's not your lungs, it must be your heart. And so what we want to do is figure out which one it really is. And how does lung disease make you short of breath? And that is the most common complaint. And if you're seeing a pulmonary specialist, he's probably giving you a little questionnaire called an MMRC, which is a kind of like the New York heart classification. It says I get short of breath when I'm doing daily activities, when I make the bed, when I walk one flight of stairs, and it helps us kind of gauge the disability of the patient based on their answer to that and the level of their lung function.
Dr. Michael Koren:
14:54
Yeah, and a couple of people raised their hand for an oxygen tank, but I think it's fair to say that the people that need to walk around with an oxygen tank are a very small percentage of all people with COPD.
Dr. Mitchell Rothstein:
15:03
Absolutely,
Dr. Michael Koren:
15:04
is that fair to say?
Dr. Mitchell Rothstein:
15:05
Yeah.
Dr. Mitchell Rothstein:
15:05
So it's when people require oxygen therapy and I'm going to show you why they do that in just a second but that means that their lung function has really deteriorated quite a bit and that you're clearly at a point 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 about cough and, excuse me, we're doing speaking of cough, but we're doing some research right now, because cough is a very common symptom. You and I were just talking about how many coughs is normal versus how many coughs a day is abnormal. It's one of those things that only crazy, nerdy people like us think about, but it's important because this can be disabling for some folks Absolutely, and there's a lot of reasons people get cough, but is COPD one of them.
Announcer:
15:59
Absolutely so. Part of COPD is chronic inflammation. With that chronic inflammation you have chronic mucus production and that mucus ends up in your airways. Those airways are innervated by nerves that are connected to your brain that induce that cough reflex. Additionally in your lungs you have something else, receptors that are called J-receptors or stretch receptors, and people that have COPD and have damaged, over-inflated lungs, those J-receptors are activated also and they cause that cough urge. So not everybody. You don't have to choke on a chicken sandwich to cough. You can cough, because there's things going on in your lung tissue chronically all the time that are activating those nerves.
Dr. Michael Koren:
16:42
And so Dr. Rothstein and I were talking about the fact that there are a lot of people out there that cough more than 15 times an hour, and it's not clear why they do that. Right, they cough less when they're sleeping, of course, but when they're awake you may clear your throat a little bit, just like a little cough or just a more prominent cough, and if you have that issue, there's a phone number you can give us a call. We can get you involved in some of the research, and this is the benefit to the patients is that we'll actually put a monitor on you to see how frequently you cough. So one of the crazy things that we do in research is really analyze the type of problems people have, and you may or may not get in the study, but you'll get the information about your cough frequency.
Dr. Mitchell Rothstein:
17:22
Absolutely. It's a fascinating study and it's the first study that's looking at a drug indicated for this specific indication. So there's no medicine out there now that's approved for chronic cough. You know we give people narcotics to slow down their cough, benzonatate to slow down their cough. None of those have been really proven to work effectively. And this is attacking this kind of neurogenic reflex that we know is active in people, and we're not including copd patients in the study right now.
Dr. Mitchell Rothstein:
17:52
First we want to see if it works on people that don't have intrinsic problems with their lungs
Dr. Michael Koren:
17:57
But the nice part of the research process, of course, is we'll help you sort it out right while you have, why you may be having that or somebody you know may have that. All right, so let's talk about the grim signals now of COPD.
Dr. Mitchell Rothstein:
18:09
So you know, and when we look at patients with COPD we kind of try to match the treatment to their symptoms, not so much their numbers. The numbers, these breathing tests we use in COPD, are basically to make a diagnosis and then, based on symptoms, is how we treat people. And the symptoms that we're primarily looking at are listed here. It's fatigue, it's shortness of breath, it's increased shortness of breath with activity, it's wheezing and mucus production, chest tightness and, like I said about COPD, it's a chronic disease and over time it's going to get worse. How quickly it gets worse, you know, nobody knows until we're following people over time it's going to get worse and can measure their symptoms and their breathing tests and see what kind of trajectory on. But we know that if you're symptomatic from COPD now left alone, it's not going to get better on its own.
Dr. Michael Koren:
19:07
So give us a little bit more insight into exactly what your lungs do on a day-to-day basis.
Dr. Mitchell Rothstein:
19:11
Yeah, Well, this is important for me because I always have to remind myself and it's always, I think, difficult for people that have COPD or don't have COPD as to what our lungs actually do. So your lungs have two operational details. Number one is to ventilate, so it moves air in and out of your lungs and it does it through these airways. So you can see the main windpipe there, your trachea, and then it divides in half into your we call main stem bronchi, and then those airways divide 23 more times until it reaches the end, aviolus, where the perfusion part starts. And if you line up all those airways, that's 1500 miles of airway that we each have in our lungs. So you can imagine if you have some mucus in all 1500 miles, it's going to increase the work of getting air past all that mucus.
Dr. Mitchell Rothstein:
20:09
And the other thing that happens is only in the main windpipe and those bronchi that come to the top are the airways supported by cartilage. After that main division, the airways are just muscular tubes, so they're like blood vessels almost. They can be easily compressed. If you breathe in real fast or breathe out real fast, they expand and collapse and that can cause problems with the air movement too. So the other thing that your lung does is this perfusion and if you go to the next slide,
Dr. Michael Koren:
20:39
there's one other thing you're leaving out.
Dr. Michael Koren:
20:41
There are two nice pillows, so that the heart is comfortable in the middle.
Dr. Mitchell Rothstein:
20:45
Well as a lung specialist you know I know the heart only has one purpose and that's to pump blood to the lungs. So as a cardiologist Dr. Koren has a different perspective on it I see it as taking up valuable lung room.
Dr. Mitchell Rothstein:
21:02
So then, once you get down to all those airways, what they end in is something called the alveolus, which you see here, and these are tiny little bubble sacks and every alveolus has a blood vessel that you can see in this diagram here, that kind of wraps around it, and there are about three or four million of these little bubble sacks in each lung and if you spread all those out it'd be 75 square meters of bubble sacks, a tennis court of bubble sacks that all these blood vessels wrap around.
Dr. Mitchell Rothstein:
21:35
And the blood that starts to come in and wraps around the 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.
Dr. Mitchell Rothstein:
21:47
So now the bloods taking this extra carbon dioxide and lower oxygen level to your lungs for the perfusion. Part of this now Interestingly and I'll be real quick with this carbon dioxide is a much more diffusible gas than oxygen is. So from the time that Blood hits that alveolus, the carbon dioxide comes out very quickly and about the first 15% of that transit time around the alveolus the oxygen takes longer about 75% of the transit time to get all the oxygen into the blood. So in the alveolus you've got the carbon dioxide coming out of the blood, the oxygen from the alveolus going into the blood, and then you blow it out. So every minute you're breathing in and out about six liters of air and every minute you're pumping about five liters of blood. And there's a little overlap on the lung side because we know the heart's not that efficient, so you have to kind of make up for that problem
Dr. Michael Koren:
22:48
the anti-cardiac Society will be calling you.
Dr. Michael Koren:
22:52
You'll be getting a letter from our 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 blood vessels are getting squeezed off or if the alveolus is getting destroyed the carbon dioxide. Usually there's enough room left for the carbon dioxide to get out, but the oxygen doesn't always have time to get in and then people need to be on supplemental oxygen. If you've lost your ability to get rid of carbon dioxide and that level's going up in your bloodstream, we call that hypercapnic respiratory failure. That's a much more serious advanced condition.
Dr. Michael Koren:
23:30
All right. So another audience question here which of the following is a test that doctors use to diagnose COPD? One spirometry, two plethysmography. Three pulse oximetry. Four tomography or five, all of the above.
Dr. Mitchell Rothstein:
23:50
Yeah well, spirometry is the test that we use to diagnose COPD. We do pulmonary function tests that include a lot of this other stuff. I don't have time to explain because Dr. Koren took up a long time. That's fine, so we'll go ahead with spirometry.
Dr. Michael Koren:
24:04
I'll give you two minutes but explain that a little bit more, because people thought it was all the above, but when you really look at the question in terms of the formal diagnosis of COPD, it's a little bit different. So go ahead.
Dr. Mitchell Rothstein:
24:17
So spirometry we're going to show you a slide about. Plethysmography is a measurement that we use to look at lung volume. So we have different volumes that we associate with our lungs. So when I take in a deep breath from resting, so I have a normal exhalation and then I take a deep breath in from that point, that's my inspiratory capacity. That's one volume. If I blow all the air out of my lungs until no more air can come out, that's my vital capacity. But even at the end of that there's still some air left in my lungs and that's called the expiratory reserve volume. And then looking at different variations on how that air comes out is part of the spirometric analysis that we use to diagnose COPD.
Dr. Mitchell Rothstein:
25:06
Pulse oximetry measures your oxygen level in your bloodstream. It's got a little bit of error involved in it. For a normal person at sea level it's about 94% plus or minus 2%. As you go up and there's less oxygen, that number obviously comes down. Tomography we don't use so much in breathing tests or in lung evaluation. So it's really the first three that are associated with lung testing and spirometry is the most important for diagnosing obstructive lung disease and why don't we go on to the next one?
Dr. Mitchell Rothstein:
25:42
So, obstructive lung disease, there's really two types. There is COPD, and then there's asthma, and then there's this condition called an overlap syndrome that has a lot of characteristics of both, but specifically with COPD, we measure the total amount of air that I can blow out from one deep inhalation. I blow the air out as fast as I can and then at six seconds, if I last that long, that total amount of air that comes out is called the forced vital capacity. Of that, the part that comes out, why don't we go to the next slide? And I can show them better. So of that, if you look at this top curve, the lines going up right, right and I'm blowing air out, that's the forced vital capacity. If you look at the amount of all that air that comes out the amount that came out in the first second, and you can see that most of it, about 80% or better, 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 very quickly at the beginning.
Dr. Mitchell Rothstein:
26:51
So when we do this spirometry test we look at your spirometry and we say how much of all the air that came out came out in the first second and if it's less than 70% that's called obstructive lung disease. And when it's less, that curve on the top, mike kind of flattens and doesn't rise up as quickly as it did on the normal patient. Now the exception to this is if you have obstructive lung disease, meaning that FEV1 was less than 70% of the total, and then we give you like an inhaler and it goes to better than 70%, you have asthma, you don't have COPD. So this is the test that tells us in large groups of people whether or not they have COPD. So an FEV1 less than 70%. And the nice part about this is you're your own control. You know we're not comparing your test to a lot of other people's tests. For this FEV1 percent test it's your total versus the amount that came out in the first second 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 the picture so if this is what your spirometry looks like, you use an 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 chest x-ray. So this is a normal chest x-ray on your left and you can see the heart silhouette. The patient is looking out at you, right shoulder, left shoulder, and you can see the heart silhouettes there. There are where that green and purple arrows are are the blood vessels in the heart, in the lungs. You can barely see them, and then these curved things on the bottom are your diaphragms. So when we breathe in, we breathe in under negative pressure, we suck air in. So when we breathe in, we expand our diaphragm so they contract and they go down. That creates negative pressure in our chest and we suck the air in.
Dr. Mitchell Rothstein:
28:52
Now, when patients develop COPD, they have this obstructive problem to airflow and they get the air never fully exhaled and they keep hyperinflating. They keep getting more and more air stuck in their chest and it leads to an x-ray that looks like that. So you can see where the diaphragm should have been, where those lines are and where they are now. You can also see the blood vessels that are going into the lungs now are very prominent because the lung tissue has been destroyed and the heart is having a difficult time pumping all that blood to the lungs again. So those blood vessels tend to develop to increased pressure. So you can experience this right now at your table If you take a breath in and then try to take another breath on top of that.
Dr. Mitchell Rothstein:
29:42
That's how that person feels all the time. Every breath is a conscious effort. They're short of breath all the time time. They don't have that room for their diaphragms to contract anymore and go down. So the differences between COPD. In general we know that both of them can have swollen, narrow airways. We know that in asthma, like we were saying, if you use that inhaler and the breathing test goes back to normal, we call that reversibility. That happens much more often in asthma. Patients with COPD may have a response to bronchodilators but they never go back to normal or else we'd call them asthmatics. We know that people with asthma, their symptoms can come and go, they can have flares of asthma. With COPD that sense of shortness of breath tends to be more constant.
Dr. Mitchell Rothstein:
30:28
In asthma because their airflow can go back to normal. We know that that's true. In COPD, it never goes back to normal. Asthmatics tend to have a younger age of onset than people with COPD, who typically develop the disease in their 40s, 50s and upward. But you can develop asthma at any age as well, and we know that the allergic background is much more prominent in asthmatics than it is in COPD patients. But we're learning that there is some type of this type 2 inflammatory allergic response in COPD patients that may have more significance than we thought.
Dr. Mitchell Rothstein:
31:06
So the goals of treatment with COPD are we can't cure it. We want to slow down the progression and we want to improve patients' abilities to engage in activities of daily living. And the key to COPD control is reducing these exacerbations, because if we can reduce those big drops in lung function, we think that will improve quality of life. So how do we do that right now? So when I was in training, most of the things I'm going to talk about weren't even in the realm of treatment options. But now we know the best thing you can do is stop smoking. That's going to help reduce that fall in your lung function and reduce cardiovascular disease and everything else that goes along with it. We have the slew of medicines that we use in COPD Pulmonary rehab, this exercise program that anybody with symptomatic COPD should go through. So symptomatic means if you have COPD and you're short of breath, even if you haven't been hospitalized, you want to go through a pulmonary rehab program. We know that that improves quality rehab program. We know that that improves quality of life. We know it reduces exacerbations and we know it reduces hospitalizations and short term it has a reduction on mortality as well. Supplemental oxygen if needed and like Dr. Koren was saying, it's less than about one. Two percent of our patients with COPD need supplemental oxygen. But if you need it it is associated with increased quality of life and increased life expectancy.
Dr. Mitchell Rothstein:
32:47
We've developed non-invasive ventilation which is kind of like you know a CPAP. You know CPAP for patients with sleep apnea. Well, we have a CPAP that can kind of act like a ventilator to help people breathe at night. That can reduce that work of breathing so people can sleep through the night if their COPD is that progressive.
Dr. Mitchell Rothstein:
33:08
We have also been doing surgeries on lungs. You've probably heard of lung volume reduction surgery. So if people have emphysema, these big blebs in their lungs, we know that we can take the bleb out and that allows normal lung that's left over to re-expand and to function more normally and that can improve their sense of dyspnea and quality of life Without doing surgery. In one of those tiny little airways we can put a one-way valve that kind of shuts the blood flow and the oxygen off to that part of the lung and that lung will collapse, essentially doing an autobulectomy. The rest of the lung will expand and improve quality of life and send some dyspnea there. And then we've also done lung transplantation in patients with primarily unilateral disease and primarily of an emphysematous type, but that's also 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 I did 20 years ago. Is that falling out of favor a little bit?
Announcer:
34:08
It's falling out of favor because of the endobronchial valves. Instead of, you know, cracking your chest open, we can down in the bronchoscopy suite, put that valve 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.
Dr. Mitchell Rothstein:
34:29
So, and then the clinical trials that are going on are addressing Medications that will improve lung function, delivery of those medicines to improve lung function, as well as a bunch of anti-inflammatory molecules that have just come out in the last decade that are having surprising results in COPD patients in terms of helping them improve lung function, reduce hospitalizations and reduce exacerbations. So the old traditional medications that we used in COPD are basically divided up into three groups. We have the beta agonist, which is like albuterol that we use in asthma. They tend to be short. There's one group that tends to be short-acting that lasts a couple, three hours, and then long-acting that can last 12 to 24 hours, and these medicines work by increasing this mediator called cyclic AMP in the muscle cell, which causes these muscle tubes to relax and they get bigger, and it's been very effective and has a relatively short onset of action. We call them rescue medicines. When it's the short-acting variety, it can give people relief within minutes. And then the next major class is these go to the next slide.
Dr. Mitchell Rothstein:
35:47
Are these anticholinergic agents, or we call them LAMAs, anti-muscarinic agents, and they're largely used in patients with COPD. Ipitropium is one that's been out for about 20 years. It's now finding a place in the use and treatment for asthma as well. And instead of actively dilating the airways, what these anticholinergic medications do is they interfere with the ability of the airways to constrict, so they relax them, but they don't actively relax them. They're very effective. Also, they come as a short-acting medication and a long-acting, a LAMA medication as well, and there's a bunch of different names for the different products there. I won't go through them because Mike used up all my time. Go on to the next slide and then we have this group of medicines called inhaled corticosteroids. So when I did my training back in 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.
Dr. Mitchell Rothstein:
36:56
We were using it in patients with asthma the marketplace and we were using it in patients with asthma and all of a sudden, instead of having an ICU full of asthma patients on ventilators and with a very high death rate, nobody was showing up to the ICU anymore because these inhaled corticosteroids were great at reducing the inflammation in the airways in these asthmatic patients and it reduced those exacerbations and the need for them to seek hospitalization.
Dr. Mitchell Rothstein:
37:25
So we translated that success in asthma patients to patients with COPD and I think you've seen widely advertised on TV and probably some of you may be even using them. We kind of combined all these groups of medicines together and now kind of standard therapy we call it triple therapy for patients with COPD is a long-acting beta agonist, that one that actively dilates the blood vessels, a long-acting muscarinic agent, which is one that prevents the airways from constricting, and an inhaled corticosteroid. And those can be very expensive and we're not sure if it's really beneficial in all COPD patients. One of the interesting things they found that when they looked at patients with COPD the patients that used inhaled corticosteroids had decreased acute myocardial events over a decade but, they had increased risks of pneumonia and upper respiratory tract infections.
Dr. Mitchell Rothstein:
38:25
So we're trying to sort that out.
Dr. Michael Koren:
38:26
So inflammatory versus pro-infection.
Dr. Mitchell Rothstein:
38:30
Absolutely
Dr. Michael Koren:
38:31
Interesting.
Dr. Mitchell Rothstein:
38:34
So these are the different kind of combinations SABA is a short-acting beta agonist used with a LABA, a long-acting beta agonist, and a LAMA, a long-acting muscarinic agent. And then you can use the triple therapy the LABA, LAMA, and ICS. Now these are all given by inhalation and one of the problems with COPD is you can't really breathe that well to begin with. So part of the problem with our therapy is if you can't actuate the device or open the device and inhale deep enough to get the medicine to your lungs, it doesn't work as well if you just go and the medicine just goes into the back of your throat. So we have a bunch of good medicines for people, but a lot of people have difficulty using them and I can tell you in my practice, every time I saw a patient for follow-up that was using inhalers, I asked them to use it in front of me just to make sure they were doing it adequately, and 50% of the time people would have their actuator and they'd show me up, they'd squeeze it. It didn't even go in their mouth and then they'd inhale and you'd say, well, we went over this, you know, three months ago, and it takes a lot of repetition if you're not doing it every day, it's a hard skill to kind of master. So over the last 15 years we've realized that there's other inflammatory components to COPD and not just treating the airway, opening and closing. Among those are these a bunch of inflammatory cytokines and alarmants. They have a huge number of different names and it's just more and more. The more I read on this, the more confused I get as to which pathway what's interfering with, the more confused I get as to which pathway what's interfering with.
Dr. Mitchell Rothstein:
40:20
Daliresp or roflumilast came out as a phosphodiesterase inhibitor type 4. So we have about six of these phosphodiesterase inhibitor types. Two of them are pertinent to your lungs, four is the most common, but there's also three. And what phosphodiesterase does is it inhibits the breakdown of cyclic AMP, which causes the blood vessels, the airways, to dilate. So these medicines reduce inflammation in the airways and they cause them to dilate a little bit.
Dr. Mitchell Rothstein:
40:52
More, recently Ensifentrine, came out and that's a PDE3 and 4 inhibitor and it seems to be much more potent than Daliresp has been and that seems to not only improve lung function but also reduce exacerbations and hospitalizations. And Ensifentrine and Dupilumab, which is a monoclonal antibody. You've probably it's called Dupixent. You've probably seen it advertised for eczema and for asthma. We now know that that medicine is also effective in COPD patients. But there's a certain type of COPD patient that that's important for, and that's patients that on their blood counts have high eosinophilic levels. Like I said before, the allergy is more common in asthma than it is in COPD, but we know that there's patients with COPD that have that allergic component and they seem to respond to this quite nicely.
Dr. Michael Koren:
41:50
Yeah, I think you told me this anecdote about how important it is to actually watch patients use the inhalers. I think you told me about this anecdote where you asked somebody to do that. The person sprayed it in the air and then put their face in the mist. So it's more than a trivial point.
Dr. Mitchell Rothstein:
42:08
I would say that in my practice and I practiced for over 30 years that my patients with COPD, one that actuated and inhaled properly was about 50%, and then of the people that did that properly, the people that could get a deep enough inhalation in to really maximally benefit from the medicine, was about 75%. So a lot of these medicines lose their power Now. Interestingly, some of these medicines are now available by nebulizer and we're going to have a study, hopefully in the next few months, that is, using a nebulizer just twice a day, using these long-acting products, so that people will actually get a benefit from their medicine.
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 out there that's looking specifically for these either eosinophilic type or non-eosinophilic type COPD patients. There's a list here of the others, some of their target compounds, and they're kind of going through this trying to find out which medicine is right for what we call them phenotype, either an eosinophilic or a non-eosinophilic dominant patient with COPD, and at least with the eosinophilic group we know that the depiction is having a marvelous effect on helping them reduce exacerbations.
Dr. Michael Koren:
43:26
Yeah, and if you want to impress your friends at a cocktail party, you'll notice that all the monoclonal antibodies end with MAB. So if somebody has an injectable drug they're using and you can tell them if it's a monoclonal antibody or not just by looking at it. Okay, well, now something important. Yeah, COPD in the cardiovascular system Go ahead.
Dr. Mitchell Rothstein:
43:46
Patients that have COPD you know it's the people that smoke a lot tend to run the risk of heart disease. So we know that. You know we're dealing with patients that often have two comorbidities they have lung disease and they have heart disease. We know that if you have an exacerbation of COPD, you're going to be at risk for having an acute myocardial or cardiovascular event as well stroke or heart attack and that as COPD progressed, when those little bubble sacks, alveoli get destroyed and the blood supply gets destroyed and the heart is still pumping that five liters per minute through the heart, but it's a smaller vascular bed those blood vessels are under increased pressure and that leads to pulmonary hypertension, which then causes more shortness of breath. An interesting fact, too, is that if you lose 10% of your forced vital capacity, your risk of 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 with anybody with a symptomatic COPD. It's a supervised classroom experience. It teaches people how to do things without putting their respiratory system under increased stress, as well as increasing their stamina, and we know that it improves quality of life, reduces breathlessness, reduces exacerbation and hospitalization rates.
Announcer:
45:09
Thanks for joining the MedEvidence! podcast. To learn more, head over to MedEvidence. com or subscribe to our podcast on your favorite podcast platform.
