Announcer:
0:00
Welcome to the MedEvidence! Podcast. This episode is a rebroadcast from a live MedEvidence! presentation.
Dr. Mitchell Rothstein:
0:06
How many of you have ever been to a talk on cough before? Somebody went to a talk on cough? Well, for the rest of you, you can now check this off your bucket list. I know this was something important for you and, to be honest, Dr. Dorman and I were talking about this before we started, and I was in clinical practice for over 30 years and Dr. Dorman so far has been in clinical practice for about eight years and about 20% of our time was spent dealing with people with cough as their chief complaint. So among the physicians and the people with experience in cough in the Jacksonville greater area, I don't think you can find two people that have had more cumulative experience with this kind of problem. And we know it's a chronic problem because, as you could all hear, there were a few of you coughing during the introduction to this. And to get started with, I think one of the things that just kind of get a feel of the temperature of the audience is I'm going to ask you a series of questions and just by raising your hand you can tell me yes or no to what you think.
Dr. Mitchell Rothstein:
1:14
So what of the following is true about cough? It's the most common chief complaint for outpatient visits. It's warm, it's a protective, life-saving, unconscious reflex. Very good, it's a good crowd. It may be the only symptom of underlying asthma. It can produce flow rates over 100 miles an hour. Not too many for that one. Or all of the above, all right. So you guys are all wise to this. It's all of the above. And it is the most common outpatient complaint for outpatient visits among specialty practices. And it is a life-saving, unconscious event.
Dr. Mitchell Rothstein:
2:05
And so the question is you know why do we cough? So in normal individuals, when something enters the upper airway and that includes the supraglottic area, the area above your larynx and the area just below your larynx and causes obstruction to airflow, it acts as a defense mechanism to prevent aspiration so that doesn't get deeper into your airways. It gets rid of foreign matter, excessive secretions and keeps us from choking to death. The reflex itself is kind of interesting. So we have receptors in our lungs, and when I say in our lungs, I mean the linings of our lungs as well as the lung tissue itself. There's a number of different receptors. There's irritant receptors, there's stretch receptors, there's receptors for thermoregulation, there's receptors for chemical sensitivity, and all those receptors add into the vagus nerve and let me see if I can get the pointer here. But you can see the vagus nerve there next to the trachea.
Dr. Mitchell Rothstein:
3:15
The vagus nerve ascends into our midbrain. So the midbrain is the portion of your brain that contains all of your autonomic function blood pressure, respiratory control, as well as the cough reflex. And as those nerve fibers enter your midbrain, which is unconscious, that then triggers the reflex to the muscles to then make you cough. And cough interestingly has three distinct phases. So when you're sitting at lunch eating a chicken salad sandwich and that piece of chicken salad goes down the wrong pipe, you don't think about it, you cough.
Dr. Mitchell Rothstein:
3:58
So when you cough there are three phases to that cough and this is reproduced over and over again. There is an inspiratory phase, and that's demonstrated with number one. Your Vocal cords open, your diaphragms contract rapidly and you take a deep inspiratory breath. This is all unconsciously. Then that's followed by a compressive phase. During the compressive phase the vocal cords close and your intercostal muscles and all your muscles of accessory respiration get activated and you generate pressure. And then, at the end of that compressive phase, your vocal cords fly open and the cough comes out with that typical sound. That we all know.
Dr. Mitchell Rothstein:
4:48
So the other interesting thing about cough is that the vagus nerve is playing the major role. There is a lot of voluntary control over the coughing mechanism itself voluntary control over the coughing mechanism itself. So if I asked you all now to cough voluntarily, you could do it. And the more interesting part about it is the physiology of the voluntary cough that you just produced is exactly the same as the reflex cough. So we know that there's some same as the reflex cough. So we know that there's some conscious part to this reflex that can then be mediated and muted or suppressed to a greater degree or imitated, like we were talking about before.
Dr. Mitchell Rothstein:
5:37
The activation of the vagus nerve that brings this sensation to your brain can be from mechanical issues like particulate matter, chemosensation, like acid reflux. We know that cold air can cause people to cough as well as warm air, and we know that pain and inflammation can also trigger this cough reflex. We know there's a lot of different receptors that all kind of feed into the vagus nerve that brings that information to your brain to initiate this cough reflex. So it's a basic reflex to save you from aspirating. It can be mimicked and muted to some degree. Aspirating. It can be mimicked and muted to some degree, and then we have what
Dr. Mitchell Rothstein:
6:32
triggers the cough to begin with, and I think at this point, Steve, if you don't mind, you can take it from there.
Dr. Steve Dorman:
6:35
So yeah, that was really beautiful guys. If you think about it, when we talk to people in clinic, most people think cough is something in the lungs or is it mucus. They think about mucinex and other things that may improve secretions. But really this is a neurologic process. It's a neurologic process and so that oftentimes gets missed by kind of non-specialist experts or the family practice clinic, the ER, the urgent care, etc. But this is a neurologic conscious but also subconscious process. So we talk about common causes of cough. There's the upper airway sinus disease, post-nasal drip, also known as upper airway cough syndrome, due to irritation in the upper airways. There's cough variant asthma. Vocal cord dysfunction is a very common cause of cough as well.
Dr. Steve Dorman:
7:33
And then non-asthmatic eosinophilic bronchitis A mouthful yeah yeah, as well as GERD, gerd, gastroesophageal reflux, and so when we're eating we have more cough after eating, usually a sign of GERD, and so when we're eating we have more cough after eating, usually a sign of GERD, you know, reflux coming up from the stomach into the esophagus, triggering that cough. So I have kids and my kids love to go to different amusement parks, theme parks. They always want to get on the carousel. Anybody have kids or grandkids in the room, right, right, yeah, so people who have chronic cough oftentimes are riding a medical carousel. You'll see the pulmonologist, like Dr. Rothstein. You'll see the allergy immunology physician, like myself. You'll see the gastroenterology physician. You may see the ENT physician. You may see the neurologist Sometimes there are habit coughs in children. They may see the psychiatrist. But yeah, it's kind of a carousel different subspecialties investigating the causes of cough inside their scope of practice. So again, the allergy immunology people. We get very excited about rhinitis, rhinosinusitis and asthma as a provocator of cough. You know the ENT people. They're very focused on polyps, chronic sinus disease, upper airway cough syndrome, vocal cord dysfunction, laryngospasm. Anything in the ears but nose and throat is kind of the main action there. The pulmonary experts Dr. Rothstein, they love bronchiectasis, COPD, bronchitis, et cetera. And then the gastroenterology people again GERD, gastroesophageal reflux .you know the slide doesn't mention but we also have, you know, the neurology people are sometimes focused on this, as well as psychiatry individuals. Those experts, thank you.
Dr. Steve Dorman:
9:40
So what happens if you're treated and your cough doesn't go away? So you're treated for your allergic rhinitis, yet your cough persists. Or treated for your gastroesophageal reflux with the appropriate therapies and the cough persists. Or you're treated for your asthma with the appropriate inhalers or biologic therapies and the cough persists. Sometimes there's not a clear, identifiable organic problem.
Dr. Steve Dorman:
10:11
By some of the specialty experts and that's really what we're focusing on is this chronic cough syndrome. So chronic cough is defined as a cough lasting at least eight weeks. It applies to people who are non-smokers, who have a normal chest x-ray and are not using an ACE inhibitor. So an ACE inhibitor is a blood pressure that's utilized many times. Excuse me, a blood pressure agent is utilized, like enalapril or lisinopril, and one of the common side effects for that specific agent is cough.
Dr. Steve Dorman:
10:44
Okay, and these are people who have cough despite adequate treatment of their underlying issues, again like reflux, rhinitis, asthma, et cetera, and so that's what the cough hypersensitivity syndrome truly is. So we'd mentioned this is a pretty robust problem. I mean I bet you didn't know that around 5% of the adult population has this. It's really underdiagnosed. It accounts for 30 million clinic visits in the US. Nationally, there's a female preponderance as opposed to males. It usually affects people in their fifth or sixth decade of life and obviously it impacts our quality of life, especially in the COVID and post COVID era. You know, I hear stories. I'm sure Dr. Rothstein has as well. I want to go to church, but nobody will sit next to me, right, right.
Dr. Mitchell Rothstein:
11:40
Or you get on the plane and the person behind you-
Dr. Steve Dorman:
11:53
Yeah, yeah I don't wanna get COVID! Yeah, or you're in the grocery store pushing the cart, a little bit of cough, and people are kind of running away, Right, I mean, these things happen. So it's a really concerning social feature. It provokes anxiety and others, it causes people to want to avoid you and it leads to social isolation. Patients oftentimes complain of symptoms like exhaustion I can't get good sleep because I'm constantly coughing. The embarrassment factor Difficulty speaking can occur, obviously, annoyance to family, friends, co-workers.
Dr. Steve Dorman:
12:27
Sometimes, with really severe coughs, there can be urinary incontinence as well as cough syncope, or you can faint due to coughing so much. Yeah, kind of crazy, but it does occur. So what is cough hypersensitivity syndrome? So again, this is a neurologic process. Cough is neurologic. The nerves become sensitized to chronic inflammation and chronic stimulation, which leads to a lower threshold that provokes the cough. This is again a neuropathic component neuropathic hypersensitivity Component, neuropathic hypersensitivity.
Dr. Steve Dorman:
13:05
So again, just another diagram reminding us that there are neuronal pathways controlling cough. And that's where you know medical experts, researchers. We try to look at the different targets on this neurologic pathway that may be manipulated to improve the cough or mute the cough. So again, this is a process that is a communication between the airways the upper airway, the lower airway sometimes, and the central nervous system or the brain. We've kind of showed this diagram in different ways but it just hammers that point home.
Dr. Steve Dorman:
13:46
There's afferent and efferent nerves and it's a feedback loop and our brain oftentimes is telling us to cough due to active firing or stimulation from external stimuli initially, but then these nerves kind of get turned on and just keep firing, provoking this cough on, and just keep firing, provoking this cough. So this increased neuronal sensitivity is due to chronic inflammation in and around nerve endings, leading to centralization. It leads to alteration of the afferent nerve terminal excitability, so these nerves are chronically on and inflamed and it leads to physical changes in the afferent and vagal neurons. So these A and C fibers and this chronic on signal leads to central conscious neurologic recognition and this is similar to other neurologic problems like chronic pain syndromes or migraine headaches or fibromyalgia, overactive bladder and then something I see from time to time in the allergy clinic another neurologic diagnosis chronic pruritus, neurologic pruritus or chronic itch.
Dr. Mitchell Rothstein:
15:01
Okay, and the same fibers that carry that itch signal are also the same fibers that are involved in this cough reflex.
Dr. Steve Dorman:
15:11
Yes.
Dr. Mitchell Rothstein:
15:11
So we're finding that in a lot of these conditions this overactivity after we've eliminated, you know, things that are treatable plays a large part in the maintenance of these chronic medical conditions for people. And we're trying to figure out kind of how to break that cycle, because it's self-fulfilling, you know, when you think about cough, cough is a violent activity. I mean, we were aerosolizing particles at 100 miles an hour. If you look in somebody's airway when they're coughing, you know their airway caliber is normally say this big. Well, when you cough, those airways slam against each other. It's like you know somebody punching you in the arm. That slamming together produces an inflammatory response and you get caught in that vicious cycle of coughing injury, inflammation, coughing, injury, inflammation. And we're trying to get out of that.
Dr. Steve Dorman:
16:07
Yeah, really it's like a snowball effect. It really is. So it may start with an organic cause leading to this chronic process like reflux. It may start with that or start with asthma, but then, after that's taken care of, the cough sensors are still on and they're firing, leading to this cough over and over and over again. So what sets off cough? Initially it is sensation in the throat, the upper chest, the larynx, and it causes this urge or this need to cough. And it causes this urge or this need to cough and it's triggered by non-tussive stimuli when these nerves are on and firing all the time, such as talking, laughing, yawning or even just randomly, and it leads to coughing fits and paroxysms that are very difficult to control in people. So the increased sensitivity to inhaled stimuli has a number of triggers. We talked about mechanical activation singing, talking, deep breathing, laughing, yawning really any moving or manipulation.
Dr. Mitchell Rothstein:
17:23
And you've probably seen people that tell a joke and they start laughing and then they start coughing again. That's that reflex kind of kicking in.
Dr. Steve Dorman:
17:32
Certainly A lot of times people will cough with weather changes. Temperature change, cold air specifically, is a pretty classic provocateur in many individuals. So chemoactivation so you go into an apartment store like Bed, bath and Beyond a lot of strong scents, right, right?
Dr. Mitchell Rothstein:
17:55
You probably see that a lot in your practice where odors? Will start people coughing. In fact, we had a no perfume policy in my office.
Dr. Steve Dorman:
18:04
Likewise.
Dr. Mitchell Rothstein:
18:04
So none of the staff was allowed to wear perfume and we told the patients before they came to the office that you know, don't wear perfume. And then you'd have guys wearing cologne and that expanded and it became all big deal. But it is, it's an issue for people.
Dr. Steve Dorman:
18:21
Yeah, it's really problematic. It really is. Certainly people get provoked by acid. They talk about spicy foods, coffee, alcohol, things that provoke acid, gastroesophageal reflux, aerosols. Again, positioning you know you're bending over or lying in a specific position and that alters the way the airway fibers, those nerves are stretching and sensing things provoking cough. So another question which of the following medications is FDA approved for the treatment of chronic cough?
Dr. Mitchell Rothstein:
18:59
So chronic cough is the key here. I'm giving you a hint when you answer this question.
Dr. Steve Dorman:
19:04
So chronic eight weeks or longer. Right so a narcotic containing medication Gabapentin.
Dr. Steve Dorman:
19:26
Baclofen, Benzonatate, or steroids, or steroids.
Dr. Mitchell Rothstein:
19:29
So who thinks? Number one codeine narcotics for chronic cough. How about number two, gabapentin. Number three baclofen. That's normally a muscle relaxant but it does have some effects on the benzonidate that is teslon pearls. That's what benzonidateis. Or steroids. Well, you did much better on the first question than you did on this question. So the answer is none.
Dr. Mitchell Rothstein:
20:03
There's no medicine approved for chronic cough.
Dr. Steve Dorman:
20:06
Yeah, it is frustrating to have a problem that there's no approved medicine for. Right, it really is.
Dr. Mitchell Rothstein:
20:19
So it was a trick question.
Dr. Steve Dorman:
20:20
Gotcha. So again, chronic cough greater than eight weeks. Non-smoker, normal chest x-ray, not on an ACE inhibitor. And so current recommendations. You know we obviously want to look into the organic causes, such as the upper airways, sinuses. Are there allergies provoking cough? We want to investigate the lungs. You know asthma as a provocateur. You know, look at things like non-asthmatic eosinophilic bronchitis or COPD, vocal cord dysfunction, as well as the obvious and common GERD or reflux, and if there's no improvement, further specialty evaluation should be indicated. It really should be so. Sometimes there's clinics where people are focused on chronic cough. Yeah, and then, you know, consider evaluation for a chronic cough study.
Dr. Mitchell Rothstein:
21:19
Like the one we're doing now. Yeah.
Dr. Steve Dorman:
21:21
Yeah, you want to take over here.
Dr. Mitchell Rothstein:
21:24
Yeah, our current study medication is an inhalational powder and we're currently looking at it in the study of patients with chronic cough and we have kind of a mantra for those of us that treat chronic cough is you want to make sure that you don't miss something bad. So when people come to see us in the office, one of their concerns, besides all the social embarrassment, is you know, do I have something bad going on? Because that's what people associate cough with. So if we've eliminated everything that we can eliminate and treated everything that we know we can treat, and you're still coughing,
Dr. Mitchell Rothstein:
22:06
We know that, as we've talked about a couple of times, this cough reflex starts in the lungs or the epithelium, the skin lining the airways or in the upper airways, the nerve fibers that travel through the vagus nerve to the central nervous system, specifically the midbrain, and we know that those fibers have specific receptors on them. And this has all been discovered in the last 20 years. So none of this was, in fact, this non-asthmatic eosinophilic bronchitis was not even a thing when I was in practice. Bronchitis was not even a thing when I was in practice, so I never treated that. But in the last 15 years we've discovered so much more about the physiology, the proteins and the genetics that are involved in disease and luckily one of them is in this cough reflex disease and how the vagus nerve works and how we can stop it from overfiring. And that's basically what Taplucanium it's a sodium stabilizer and when the nerves are inflamed, the nerves themselves open up these pores and these proteins come in through these pores and stimulate the nerve to depolarize, to fire, and if we can block that from happening, we can shut down the firing rate of the nerve.
Dr. Mitchell Rothstein:
23:39
Now these nerve receptors, these sodium channels, are found everywhere in our body, even on blood cells that are circulating in our bloodstream, and specifically, we've been able to identify when I say we, I mean all these brilliant scientists at research universities have been specifically able to identify 10 different sodium channels and of those 10, there's three that are predominant in this nociceptive cough vagus nerve fiber.
Dr. Mitchell Rothstein:
24:14
And we know that this Taplucanium , which is very similar to lidocaine, which covers out all these 10 sodium channels, this one only is localizing the three found in the vagus nerve that's involved in this cough reflex. So the theory is that if it works and if we're right and if we can reduce that hypersensitivity and hyperactivity of the vagus nerve, we can shut down that urge that our brain starts to get to cough. And for people that don't have any other serious medical problems and that the things that we know cause cough are adequately treated, we can at least provide symptomatic relief, and sometimes symptomatic relief is all you can do. So that's what the theory behind this medication is and the study that we're currently doing.
Dr. Steve Dorman:
25:12
So think about cough as a light and the electricity is going to the light. We're trying to turn that signal off. We're trying to shut the light off at the switch with that medicine. That's what this is doing.
Dr. Mitchell Rothstein:
25:27
And the other thing that I'll add I know in my practice, and I'm sure Dr. Dorman and yours, a lot of times people are dragged in to see us for cough or for snoring or whatever, and they're not bringing us, but everybody that they've been annoying for the last 10 years has forced them to come to see the doctor. So if you have, an annoying cougher that you know. Urge them to get it taken care of, to go see a doctor and then consider being in a study.
Announcer:
25:54
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