This webinar was recorded on November 17, 2022
Some coughs last longer than a week or even a month. Join our discussion with Dr. Wesley Sublett as we discuss the causes, implications and treatments for a long term cough.
Speaker:
- Dr. J. Wesley Sublett
Sponsored by the American College of Allergy, Asthma and Immunology
Transcript:
This transcript is automatically generated. While this transcript is believed to be accurate, errors sometimes occur. It remains your responsibility to evaluate the accuracy and completeness of the information in this transcript. This transcript is not intended to substitute for professional medical advice.
Speaker 1 (00:04)
This is Sally. Schoessler, Director of Education for Allergy and Asthma Network. Today’s Webinar helps allergy and Asthma Network live out our mission to end the needless death and suffering due to asthma, allergies and related conditions through outreach, education, advocacy, and research. A cough is not an unusual thing at this time of year, but it can be caused by so many different things. And what do we do when the cough doesn’t go away, but hangs on and on? Well, Dr. J. Wesley Sublett is with us today to share some vital information on chronic cough. J. Wesley Sublett, Md MPH. is a partner and medical director of clinical research at Family Allergy and Asthma based in Louisville, Kentucky, with multiple offices throughout Kentucky, Arkansas, Indiana, Ohio and Tennessee. He’s a graduate of St. Louis University and the University of Louisville School of Medicine Board, certified in both pediatrics and allergy and immunology. Dr. Sublett completed his internship and residency in pediatrics at the University of Louisville Kosair Children’s Hospital. He completed his fellowship in allergy, asthma and immunology at the University of Cincinnati. Recently, Dr. Sublett had served on the American College of Allergy Asthma Immunology Board of Regents, president of the Greater Louisville Allergy Society and the chair of the college’s Drug and Anaphylaxis Committee.
Speaker 1 (01:31)
Thank you so much for being with us today, Dr. Sublett. We’re really looking forward to your presentation today.
Speaker 2 (01:38)
Well, thank you Sally. Thank you for the introduction. And these are my disclosures that are listed on the screen for those in the audience. I do have multiple conflicts, but the only one that would really be pertinent to today would be Bellas, which is in development of a drug for chronic cough. So today’s learning objectives for today’s Webinar. We’re going to start by understanding the epidemiology and impact of patient quality of life and chronic cough. We’re going to learn how to formulate an appropriate evaluation and treatment for patients with chronic cough. And lastly, we’re going to be able to explain current and emerging treatments for chronic cough at the end of this webinar. So let’s start by really understanding what is a cough. Well, first, it’s one of the defensive reflexes of the respiratory tract. Cough can be elicited from the larynx, the trachea or the bronchi. And it is clearly defined by really three phases. The first is an inventory effort, which is called the inventory phase, which is followed by a forced expiratory phase against a closed glottis, which is the compressive phase of cough, followed by the opening of the glottis and rapid expiration and airflow, which is the explosive phase.
Speaker 2 (03:18)
So it’s a complex mechanism to help protect us, especially from particles and irritants in the lung. So when we look at cough and especially chronic cough, we know that there’s multiple mechanisms involved in the generation of cough. And neural pathways contribute a lot to the generation of cough, especially the central bagel system. Vagal sensory neurons are involved in cough and they enervate the larynx, the trachea and the main bronchi and possibly even the lung parenchyma. Vagal fibers, depending on which type of vagal fibers we’re talking about, can be activated by mechanical stimuli such as inhaled particles, mucus even aspirated gastric contents, or they could be activated again depending on the type of vague fibers we’re talking about by irritants and inflammatory mediators. Vagal fibers involved in cough express several ion channels and receptors needed for transduction of diverse sensory stimuli and lead to the formation and conjunction that regulate action potentials to the brainstorm nuclei to coordinate cop motor patterning. Because of this, we know that central neurophysiology is an important component of all and that’s going to, as we’ll discuss later on, be an important target for the treatment of chronic cough in the brain.
Speaker 2 (05:09)
There’s actually some distinct networks that are involved with the regulation of cough that encode the urge to cough and for the cognitive and the effective processing that are involved with cough as well. So, lots of nerve pathways that are involved with cough and potentially lead to chronic cough, it’s more than just the central pathways. We know that there’s immune modulation of neurons that are involved, especially in chronic cough. So, when we look at coffee, a wide variety of receptors and the immune mediators are expressed on the vagal sensory neuron terminals which when activated to pull our husband or terminal producing a potential that is sent to the brain. Some generated potentials will reach the threshold needed to directly fire and go on to the brain, but some will leave the nerve terminal and lead to being more responsive secondary to inoculate stimuli, which is really important especially in chronic cough and the idea of cough hypersensitivity. Not all cough invoking sensory neurons express the same gamut or the same number of immune receptors on their surface. And there’s currently research to define which receptors are most important in the increase in signaling among the vagal nerve, as well as which neuroimmune.
Speaker 2 (06:54)
Allergy pathways are important, especially in chronic cough. We know that there are mediators released during tissue inflammation that modify sensory neurons and actively induce long term neuroplastic changes in the sensory neuron structure. And this leads to an amplification of neuropathways that are probably very important in chronic health. This is typified by a family of neurotrophic factors, notably neuro factor and neurotrophic factor that are produced by many inflammatory cells that lead to vaginal nerve upregulation on its surface. When these neurotrans factors are up regulated, it leads to transcriptional upregulation of certain proteins, some of which are novel, that maybe not normally express, which leads to the promotion of neuronal sprouting, leading to an increase in the density of nerve processes in the inert target tissues. And so this neuroplasticity or this up regulation of neuron factors has been likened to the same type of events that we see in the development of chronic pain. So cough is more than just the lung. We now know that it has to do with a lot of immune regulation on the actual vagal and sensory nerves that inherit the trachea, the long paringa and the larynx. So the idea of central sensitisation and chronic cough is where not only do the peripheral vaginal nerves get upgraded by the immune modulated agents that are released during inflammation, but we also know that there may be some inflammation, some upregulation within the central nervous system itself.
Speaker 2 (09:20)
And the central sensitization is a central nervous system process that amplifies these peripheral sensory inputs that are coming in from the vagal system. During lung inflammation, the heightened sensory nerve activity are transmitted to the brain stem and drive higher than normal synaptic activity. And over time this results in recruitment and or activation of other neuroglial cells such as astrocytes, microglia and oligodendrocytes. And this really leads to further amplification and further effects on the synaptic transmission of cough signaling. And so with neuroinflammation we get an increase in excitatory neurotransmission with a decrease inhibitory effect leading to central neural circuits really up regulating the responses from the periphery that lead to chronic cough. At least that’s the current thoughts. So how do we define cough when we’re seeing it in the clinic? We currently define it based on duration and that duration is how we are going to define cough for today. So for acute cough, acute cough is really a cough that is less than three weeks in duration. The most common causes that we see of acute cough are due to respiratory infections. Most are going to be viral in nature followed by exacerbations of underlying diseases such as asthma, COPD and pneumonia.
Speaker 2 (11:18)
For substitute cough, this is going to be defined as a cough that lasts anywhere from greater than three up to eight weeks in duration. And the most common causes of subacute cough or postinfectious cough, which again we see mainly with viral illness or exacerbations of underlying respiratory diseases such as asthma, COPD. And occasionally we’ll see upper airway cough syndrome or what most people know as postnasal drip induced cough that can last anywhere from three to eight weeks. Lastly, and what we’re talking about mainly today as chronic cough, chronic cough is going to be defined as a cough that is greater than eight weeks in duration. And this is caused by really the top four are going to be upper airway cough syndrome, asthma, gastric reflux, gastroesophageal reflux disease and nonasthmatic eosinophilic bronchitis. And those are going to lead to the four most common reasons we see chronic cough we’ll look at a little bit later that not everybody will fit in those four and that’s really where sending someone to a cough center is really important. So globally, when we look at chronic cough, again cough that’s been defined by duration of eight weeks or greater, we see that the overall prevalence of chronic cough worldwide is about 9.6%. If you look at the map that’s shown on the screen and the statistics that are on the left hand side of the screen, you’ll notice that chronic cough is significantly seen with far more prevalence in Oceania which would be mainly Australia, Europe and America compared to Asia and Africa, which have chronic health, is less prevalent in Asia and Africa.
Speaker 2 (13:33)
When you look here in the US. Shown on the screen is a study that looked at trying to gain the prevalence of chronic cough here in the US. It was based on the 2018 National Health and Wellness Survey and out of approximately 75,000 respondents, it was shown that the prevalence of chronic cough was around. If you look at how it was distributed in our population here in the US, chronic cough we’re seeing in older individuals and we’re predominantly female compared to those that did not have chronic cough. Now, chronic cough is a significant healthcare burden. It is one of the major reasons that patients seek ambulatory care here in the US. So cough is one of the most frequent reasons that over the National Health Statistics reports that we see it’s usually in the top five. Here on the screen is a report looking at the National Healthcare Statistics, looking at inventory visits in 2007, even though it was reported out in 2010 and approximately 2.8% of people reported cough as a reason they were seeking care or seeking an office visit. Now, if you look at 2018 it was very similar that’s the most recent data we have for ambulatory care and it was about 2.1% of visits.
Speaker 2 (15:29)
So it’s a consistent top reason patient seek healthcare provider office visits and probably will continue especially as we get into the post covered years. Chronic cough, as we’ve seen on the previous site, is a major reason patients seek medical treatment, but it’s really a large spectrum of why they’re seeking care. Many patients with chronic cough really become socially isolated due to fear of coughing severely in public places. The patients also are very distressed because this may indicate they have something else going on. They’re worried about further exacerbating other negative effects either on relationships with their co workers or family members and especially in a post coveted environment. The pandemic really has created major constraints on social life and individuals that have chronic cough because of that stigma of coughing associated with a respiratory illness such as coronavirus. And this has resulted in further psychological anxiety and stress. So if you look at how our patients are impacted and how they’re impacted specifically in quality of life on the screen is a scoring system called the Sickness Impact Profile. And as a reference point, individuals that have no health related dysfunction should score close to zero.
Speaker 2 (17:25)
So these are patients that have chronic cough and if you look across that graph, they have meaningful adverse psychological and physical effects on their quality of life due to chronic cough compared with individuals with no health related dysfunction. Baseline Sip scores show that there’s an associated increase of dysfunction greater than usual on daily activities, particularly in categories of ambulation, social interaction, sleep work, home management and recreation. And the asterisks on the screen are comparing chronic cough with other disabled patients with chronic respiratory disease. So as you can see, these scores really relate to someone that has more of a chronic disabled pattern where the normal population should have close to zero sip scoring. And so our patients with chronic cough are highly impacted in multiple areas of their life and greatly affects their quality of life. This has been repeated multiple times looking at chronic cough and how it impacts quality of life. This was a study looking at chronic cough compared to those that didn’t have chronic cough and just looking at just a routine quality of life scoring or the standard form 36 those patients that had chronic health scored significantly lower when compared to patients without chronic cough and both physical and the mental component of the SF 36.
Speaker 2 (19:34)
Those patients with chronic cough also show higher incidence of anxiety when compared to those patients that don’t have chronic calf, and they also show a significant increase in depression compared to those that don’t have chronic health. So it greatly impacts their quality of life, it leads to other mental health conditions such as anxiety and depression. And it’s just something that we need to think about when we are seeing these patients clinically in our office. As you can imagine, not only is their mental health affected and their quality of life, but one of the major things that we know affects both mental health and quality of life is sleep. And so when you look at patients with and without cough, especially chronic cough, those patients that have chronic cough in all areas of sleep have a significant impairment when compared to those that do not. And this includes difficulty falling asleep. They wake up multiple times a night, they’re waking up too early, they qualify, their sleep is poor. And so this leads to other probably stressors in that patient’s life. Besides being an economic burden on our patient, we know that it probably leads to an economic burden in our society due to chronic cough.
Speaker 2 (21:16)
And so when you look at long patients that are employed with chronic cough, those that have chronic cough report greater absenteeism 13.6% compared to those that don’t have chronic cough at 6.6%. So there’s a greater absenteeism in chronic cough compared to normal. They also report a greater presenteeism as well. And presenteeism is just the percentage of hours of impaired performance due to a disease. So when you compare presenteeism, 34.9% of patients with chronic cough compared to those without chronic cough at 19.5% report it just greatly impacts their work style due to chronic cough, leading to work productivity loss. So 42% of patients with chronic cough compared to 22.4 in the normal population. So it affects not only the patient, but it affects just the general kind of work environment, economic environment here in the US. Due to chronic call. So the good news is we’ve had in the recent years we’ve had some advances in chronic call. The guideline that I like to point to is a guideline that was published by Chess. It’s the chest guideline and expert panel report for chronic cough. And on the screen is an algorithm that is published in that report for chronic cough and for the management of patients greater than 15 for chronic cough.
Speaker 2 (23:15)
I would recommend anybody that has seen patients with chronic cough look at this expert panel report and really get to know it because it really is a very good way to work up a patient with chronic call. And we’re going to go through a little bit in just a minute. So how should we start all evaluations of call? Well, number one is we’ve got to take a detailed history. We need to know how long they’ve had a call. I like to qualify their call. Is it productive? Is it dry? Is it a mixture? What are the triggers that cause their cough? Environmental exposures and occupational exposures are some of the biggest clues we can have in the treatment of call in dealing with chronic cough. We really need to know what previous evaluations have been done. We need to know what testing has been done, who they have seen. I always like to try personally to try to get those reports because while patients report evaluations, sometimes there is a half evaluation. And so we really, especially in the realm of chronic cough, we really need to know what has been done and potentially repeat some of these tests before going on to treatment of chronic cough that is not responsive to traditional therapies previous treatments and treatment duration.
Speaker 2 (24:52)
It’s extremely important. We know that while gerd is a significant cause of chronic cough, many times it is either under treated with the inappropriate amount of PPI or for not long enough duration. It’s also important to know their current medications. We know that Ace inhibitors have greatly been associated with chronic dry cough. And so I always want to know what medications are they currently taking when assessing chronic cough. There’s many ways to assess a call when we’re assessing cough. We really need to look at three different things. We need to assess our cough severity and research. We really have two really good ways of assessing cough severity. The first is through the cough visual analog scale, which is an analog scale that the patient fills out to determine visually how severe their cough is. The premium ladder is also a kind of a visual scale to look at cough severity. Cough quality of life is important. We’ve already seen previously that quality of life is greatly impacted in these patients. Leicester Cough Questionnaire there actually is a cough quality of life questionnaire now available. Again, most of these are going to be done in research, but they are attainable especially quality of life scores and you could utilize them in your own practice if you’re assessing cough.
Speaker 2 (26:44)
Now, cough frequency is going to be a little bit more difficult to do in the clinical setting. Most of what we have available to assess cough frequency is done in research. The Leicester Cough monitor, which is a lapel microphone which has been modified over the ages, and the vital Jack, which is also very similar, is something that we use in research to measure cough frequency. They actually can record the number of coughs the patient is having in an hour. That is more important in clinical research. And these are devices that are sometimes hard to obtain and could be cost prohibitive depending on the clinic. But there’s new technology that is being developed, one of which is potentially on the iPhone using their smartphone to record their calls while either they are awake or asleep, so that we can actually have a measurement of cost. But these technologies have not been validated and stolen development for today. So, as we alluded to earlier, there are the four most common causes of chronic cough or on the screen, the most common being the upper airway cough syndrome. And these are usually due to various rhinitis conditions. And so in evaluation of upper airway car syndrome, it’s usually important to have attained a sinus et.
Speaker 2 (28:23)
Hopefully I have a really good rhinologist in my area, so I usually will coordinate here with the rhinologist to get nasopharyngeal scope to do so. We can assess not only the nasal passages and sinuses, but also to assess their larynx. And lastly, something that I do, which is an allergy evaluation. Allergic causes and upper airway cost syndrome are important, and these two can be connected back to your history, especially if you have good environmental history with a possible trigger, either occupationally or at home, as was an important and the second most common reason patients will have chronic cough. Obviously, those that are on the line probably are very familiar with how to assess asthma, but just know that we should obtain spirometry with reversibility. I’m lucky enough to have FENO here in my office. I find FENO is an important part of evaluation of asthma. It’s an adjunctive tool that we can use to assess every inflammation. And lastly, if we have questionable spirometry results without reversibility, we may need to go on to more of a provocative test such as the Methacholine challenge to really assess airway hyperresponsiveness to rule out asthma, non asthmatic, eosinophilic bronchitis, it’s a little bit more difficult.
Speaker 2 (30:13)
My pulmonary colleagues and I coordinate on some of these patients. We do see that FENO is elevated in these patients that have escaped or a bronchitis. So these are going to be patients that maybe my office do not show the normal characteristics of asthma, do not show reversibility on their spirometry, have a history of a very productive cough. I do have an elevated FENO. I personally do not do induced freedoms in my office outside of research, but my pulmonology colleagues will many times do bronchoscopy or to induce feedback to assess for Eosinophilic bronchitis. A chest CT could be helpful in initially diagnosing these patients, but it’s really that induced or bronchial is going to help us determine that this is truly eosinophilic bronchitis. Lastly, it’s something that I feel like I see a lot of in my clinic, which is gastroesophageal reflux disease. As an allergist, I find that there are many patients, especially with cough, that are be sent for asthma evaluation, that really have gastrosoft reflux diseases that are common cause of their call. And just know that if you obviously history is very important, but it really requires a trial of a high dose PPI, preferably done bid for eight to ten weeks and lifestyle modifications.
Speaker 2 (31:58)
And if you have a good gastroenterologist colleague, getting an EGD is really diagnostic for gastrosoft reflux disease. But those are going to be some evaluations you could do for the most common reasons. We see chronic cough with an identifiable cause. Obviously, based on the chest guidelines which were shown previously, there are some red flags we should be very aware of. Hypothesis is a red flag that needs to be worked up and that can really signify a more insidious condition. Anybody that has a smoking history, especially those that have a 30 pack history, who really needs to be evaluated for lung cancer, hopefully with the chest CT, smokers with nuanced cough and changes in voice, should also be evaluated aggressively. If you have anybody that is having reoccurring pneumonia, any type of systemic symptoms, fever, weight loss, peripheral edema, weight gain, we need to assess other causes of their chronic cough, whether it’s immunodeficiency, whether it’s some type of cancer. There are many reasons people can develop chronic cough, but these red flags should be reasons to really be concerned about a much more insidious problem. Outside of the four most common reasons people get chronic cough and that requires a much greater work up.
Speaker 2 (33:59)
So do not forget about the red flags when assessing chronic cough. So we know that chronic cough is going to be eight weeks in duration or greater, but it can really be defined as one or two things. If you’re able to have an associated or underlying medical condition that can be identified and treated per guidelines, but the cough persists, we can really define that as refractory chronic cough. If you’ve identified a reason but they don’t respond to that traditional medical therapy, then we can define it as refractory conic call. However, there are times where we have gone through all the algorithms, all the assessments we can think of, and we still cannot really adequately define a medical condition that’s causing their call. And in that case, we call that unexplained chronic call. And that’s really a box you don’t really want to be on because that probably has to do with that neural hypersensitivity call that we just don’t have a great treatment, nor do we have a good way of diagnosing to date. So it is really of utmost importance to perform an extensive and thorough evaluation of reversible causes of cough before proceeding on to the treatment of chronic cough, which we’ll get to, we need to make sure we are eliminating all potential causes of reversible cough before moving on to what we’re going to talk about next.
Speaker 2 (35:52)
So currently there is no drug approved for chronic cough. It’s a major deficiency we have currently, but hopefully in the near future that’s going to change. I always find it very interesting. I do clinical research and I find it interesting when I talk about multiple drugs, when certain drugs are developed, especially in chronic cough. I find this an interesting fact, really. The last novel anti Tessa agent approved by the FDA was benzonatate, and that was in 58. We got Tessalon or benzonatate, and we haven’t had anything since. So we’re going on it’s a long time since we’ve had any really anti agent available for our patients. So now that we’ve identified, OK, someone has chronic cough, we can’t identify a cause. What are some of the therapies we could think about to treat our patient with chronic cough without an underlying without an underlying cause on the screen? You have to remember, we don’t have an FDA approved treatment. So all of these treatments we’re going to be talking about are going to be off label. So Amitriptyline, Gabapentin, speech therapy and narcotics have all been tried with chronic cough. Again, these are all off label treatments for chronic cough and it’s important to remember that.
Speaker 2 (37:55)
But we’re going to kind of look through some of the literature that is available in the treatment, chronic cough for each one of these. And we’re going to start with amitriptyline. So most of these treatments that were shown in the previous screen have very few placebo controlled studies that were done. And really for Amitriptyline, there is not a placebo controlled study, double bond, placebo controlled study for amitriptyline any chronic cough. But this was a study that was reported out in 2016 by Duke Voice Care Center, where they in the past use a lot of amitriptyline. It was a retrospective chart review of adult patients treated for chronic cough with amateur pulmonary two to three year period. If you look at their cohort, 89% of patients that were taking the medication at their first clinical follow up at around three months, 67% were still taking it, with a improvement of their chronic health. At that time, there wasn’t any statistical syndicate predictors of cough improvement with medication that were identified. And then these patients were followed over several years. And probably most importantly, at year two or three, they did a look back and of those that had chronic cough that were treated with amitriptyline.
Speaker 2 (39:43)
53% reported that they had a greater than 50% improvement in their cost. But only about a third of them, 34%, were still taking their amitriptyline. Also, about 65% of their patients had titrated the medication to effect. Some had actually restarted. About a third had restarted their amitriptyline. So it looks like amitriptyline may play a role in chronic cough based on this data, but it is still something that we need to investigate further. I will say the most reported reason that patients stopped was because of side effects, especially dry mouth. So just remember that when treating chronic cough with amitriptyline, as you titrate up, you’re going to see more side effects with medication increase. Well, what about Gabapentin? Well, there is a randomized, double bind, placebo controlled study looking at Gabapentin and chronic cough. This was done in Australia. This was a randomized, double blind, placebo controlled trial that was done in adults with refractory cough without any identifier respiratory disease or infection that were either randomly assigned to receive Gabapentin or placebo over a ten week period. These patients were initially prescribed Gabapentin and actually went through a six day dose escalation to achieve 1800 milligrams of Gabapentin, which they continued for a ten week period of time, or they were on placebo.
Speaker 2 (41:39)
And if you look on the screen, we’re really looking at several components, but the most important is in the very middle, which is that visit three. So visit three is when they had been on that maximum dose of Gabapentin for a period. At that point, they had been on it for about six weeks. And so that was when they were kind of going to see their maximal efficacy. And so at that time, they were looking at several different components. So at that time point, Gabapentin was led to a greater improvement in LCQ, which is that Leicester quality of life score for cough compared to placebo. There was a significant difference there. There was a significant difference in cough severity that was assessed by visual analog scaling when compared to placebo, and there was a significant reduction in cough frequency compared to placebo at that visit three, which is again about ten weeks into treatment. Interestingly, there was no difference between Gabapentin or placebo when they looked at cough reflex sensitivity that was quantified using capsaicin. So that bottom right or CRS scoring, there was no significant difference when they were inducing cough with Kepsanison compared to placebo.
Speaker 2 (43:37)
So while it looks like quality of life and cough frequency is affected, it was not effect, it did not affect inducing the cough through an irritant such as capsaicin. So obviously, a treatment that I utilize a lot in the treatment of chronic cough, and especially for evaluation, especially for the vocal cords, is speech pathology. And I do think that speech pathology plays a role in the treatment chronic cough, even when we were talking about conditions outside of paradoxical vocal core movements or DCD. So this. Was a double blind, placebo controlled style looking at speech pathology that was done in Australia and it’s a single, it was looking at those patients that were on chronic cough that received therapy versus not. And these patients were either randomized, received no intervention, or at least attend four interventional sessions with a qualified speech pathologist. Now, interestingly, both groups, both the placebo group with no intervention and those that did have treatment, both groups showed improvement over time in the trial of their call, but the magnitude of improvement was significantly greater in the treatment group that had speech therapy for four interventions compared to those that did not.
Speaker 2 (45:29)
And this is a significant reduction in all symptoms scores after the intervention was greater compared to placebo speech pathology. Treatment really consists of four major components. The first really is education. I have found that working with my speech therapists colleagues, they really can communicate with our patients about the mechanisms of cough, the mechanisms of abnormal laryngeal movement, and they really will help the patient understand by doing speech therapy, what are the goals and what is the rationale of doing speech therapy in the treatment of cough? They teach cough suppressive strategies, including laryngeal repositioning techniques. They really do a great job in communicating with our patients about reducing laryngeal irritation and this is by reducing exposure of the larynx to alcohol reflux, mouth breathing, oral breathing. They talk about improved hydration, they talk about reducing photochromatic vocal behaviors. And I find that at the end of that, patients really come away with a group of strategies to help their chronic health and then they do a lot of psycho educational counseling addressing, you know, why are we doing speech therapy, dressing, motivation, addressing adherence. And these really do lead to an improvement in chronic cough as shown by the previous slide.
Speaker 2 (47:21)
So lastly, and this is probably a treatment that I do not utilize as often, but there have been reports of using opiates in chronic hall and this was a study that was done in the UK. It was a randomized, double blind, placebo controlled study over four weeks of slow release morphine, five milligrams bid and a corresponding match placebo. And their cough was assessed using the Leicester Cough questionnaire along with daily symptom diary. And as we saw, there are cough challenge such as capsaicin. In this particular study, they actually used citric acid as a cough challenge, as an irritant and these were used at the time of over that at the end of that four week period on their morphine sulfate or on their placebo. It’s a pretty small study. It was 27 patients that completed the study, but they did see a significant reduction compared to baseline of their live chest or cloth questionnaire compared to placebo. For patients that were enrolled in the morphine five milligram group, there was a rapid and highly significant reduction by 40%. And daily cough scores among those patients that were on the slow release morphine. However, when they did objective testing, again using irritants, in this case citric acid, there was no significant change in citric acid concentration that compared to placebo that induced cough.
Speaker 2 (49:17)
So we’re going to kind of start to wrap up and move on to questions. But there are some potential therapies that hopefully will be available in the future for chronic health. Again, currently there are no FDA approved therapies on the market for chronic cough. Those are in development. The P2X3 antagonists are the furthest along in drug development. We know that the P2X3 e receptor is an important component of the mechanism of cough induction and the P2X3 antagonists are being developed to block that initiation of reflexes and hopefully will be a component we’re going to talk about in the near future in the treatment of chronic cough. There are other programs are not nearly as far along as the P2X3 antagonist. We know that there are though the NK one or the neurotrans one receptor antagonists that are in development. These drugs could potentially play an effect on both peripheral and central effects of cough. And most interestingly say there is also the voltage gated so doing channel blockers and the TRPM antagonist that are also in development. But these are not nearly as far along in clinical research development as the Ptux three antagonist.
Speaker 2 (51:01)
There has been at least one of the P2X3 receptor antagonists that have presented their phase three trial data to the FDA. Gefapixent is an oral P2X3 receptor antagonist that was submitted to the FDA but did not get approval to date. The FDA came back and asked some further questions of the company before and those are being investigated currently. But the key pivotal trials for Gefapixent are on the screen. So cough one and cough two were both double blind, randomized parallel groups, placebo controlled phase three trials looking at chronic cough and those patients 18 or older who had to have had at least a year or more of chronic cough to be included. There was actually three treatment groups either placebo, Gefapixent, 15 milligrams bid, Gefapixent 45 milligrams bid. And at the end of either cough one, which is a twelve week program, or call two, which was over 24 weeks, really they looked at called frequency. And at least with Gefapixent 45 milligrams PID, it did show a significant reduction in cough frequency compared to placebo in the twelve week study or cough one, there was an 18.5% reduction compared to baseline.
Speaker 2 (53:05)
In the 24 weeks it was 14.6 compared to placebo of notebooks, 50 milligrams bid did not show any significant reduction in cough frequency compared to placebo and either study. Gefapixent it did at least in the top two, there were some adverse effects that were related to taste of service. These are going to be with anything that has been reported in the past, anything with P2X3 receptor antagonists. We know that taste of Gefapixent is something that is going to be associated with that class of medications and so I think kind of ending up here. Just as a note, again, there is no FDA approved therapy at the date for chronic cough, but hopefully in the near future, especially with some of the clinical programs that are involved, but hopefully we will have solutions for our patients that do experience chronic cough. But it’s utmost importance that we really do a thorough investigation of reversible causes of chronic cough and adequately treat those reversible causes before going on to treatments of refractory chronic cough. And with that, I’ll take some questions to kind of wrap up the webinar for today.
Speaker 1 (54:43)
Wonderful. Thank you so much, Dr. Sublet. We do have some great questions and we’ll get to those as quickly now here as we can. Our first question is from a school nurse who’s asking that with coughing in COVID, when an elementary school students return to school after being ill, how long should we be keeping an eye on signs and symptoms and suspecting Long COVID?
Speaker 2 (55:08)
Well, yes, so long. COVID OK, that’s a great question. So Long Covid and cough. I haven’t specifically looked at cough. I know that with any viral illness such as influenza, RSV, which we’re seeing our local area at a pretty high rate right now. And COVID all of these really can cause not only acute cough, which is that cough less than three weeks, but they can move into more of the subacute process that last anywhere from three up to eight weeks. And so I would always say if you have a child that is since this is a school nurse asking this question, anybody that has a child that has a chronic call greater than eight weeks, they really need to see a specialist to assess what could be causing their cough. But it’s not uncommon for chronic cough to be caused by any respiratory illness such as code.
Speaker 1 (56:21)
Thank you so much. We have a patient who lives in New York and has a mold and a grass allergy, but they’ve been coughing that she says for years. Where is there a cough center? I mean, she’s not asking you to tell her a specific center, I don’t think. But how does someone find a cop center if they need that kind of treatment?
Speaker 2 (56:38)
Yeah, that’s a great question. I will say there is. If you’re in New York, there is someone very well known that works on chronic cough. But finding a cough center is not like picking up the phone book or googling it. There is no certification, but there are definitely areas that people do have an interest in chronic cough. And so if you already have a specialist, I would talk to them about helping you find that center that may help you with your evaluation of chronic cough. Or making sure that your current provider is really addressing all those potential reasons people can have chronic cough.
Speaker 1 (57:36)
Thank you. Should people with a dry cough be seen by a gastrointestinal physician?
Speaker 2 (57:44)
Well, I think that there’s many specialists that could be a starting point for chronic cough. I think allergies and immunologists do a great job in assessing chronic cough. I think my pulmonary colleagues do a great job in assessing chronic cough. I think that my ENT colleagues, they have a place that they start and looking at chronic off. And so hopefully we are in environments that we can have this team approach where whether it’s an allergist, a pulmonologist, an ENT, or a gastroenterologist or potentially even a speech therapist that we really coordinate care to make sure we’re addressing every potential reason for reversible causes of chronic cough.
Speaker 1 (58:41)
Okay, thank you for that. Our next question we got a couple more our next question is how does vocal cord dysfunction rank in cases of cough?
Speaker 2 (58:52)
Yeah, great question. It’s actually not in the top four, which is surprising, I know, to most people that are on the line, but it’s definitely part of my evaluation. But it doesn’t rank in the top four for reasons of chronic health. Now, is the research and the meta analysis that led to that conclusion, could there be a deficiency in our data and our research? Absolutely. And I do think that as evident by treatments of chronic cough, utilizing speech therapist and speech pathologist as a part of the team of evaluation of chronic cough is important. It’s just interesting that BCB or paradox and vocal corporate is not in the current top four for the treatment or for chronic call.
Speaker 1 (59:53)
Okay, thank you. The next question is, with little in the way of treatment, shouldn’t share decision making be a central part of this evaluation and treatment?
Speaker 2 (01:00:03)
Well, other than saying absolutely or yes, I mean, I think any treatments we do with our patients, there should be a component of shared decision making. I think what is important with shared decision making, at least in the sense of chronic cough, I think many patients that I see personally and this is based on my own biases and my own personal experience many of these patients have seen multiple providers and have tried multiple treatments. Maybe not adequate or adequate dosing or adequate duration. And so while I absolutely agree with your decision making, I think when it comes to especially refractory call, we need to really look at this as an algorithm. We’re making sure that we are going through a stepwise process and addressing not only what the patient is concerned about, which is our cost, but making sure we’re adequately addressing that algorithm as well, to make sure we’re not. Missing. Moving on to, again, that kind of late treatment, which are going to be those unapproved treatments. Non FDA approved treatments of chronic calf. And so make a long story short, I utilize shared decision making all the time. But for instance, many of my patients I’ve seen may have been treated for GERD, but may have not been treated a long enough duration, or b, at a high enough dose is recorded in the chronic cough literature as being adequate.
Speaker 2 (01:01:50)
So they really require like, uma, resolve 40 milligrams bid for at least ten weeks to be adequately assessed for chronic cough related to GERD.
Speaker 1 (01:02:04)
Okay, as we move on, we have one more question for one more question, one comment. Somebody is saying that they’re hearing lots of questions and complaints of new onset chronic post COVID19 with no underlying issues. Is there any interventions that have a clear advantage over any other treatment for this?
Speaker 2 (01:02:25)
Well, I definitely think that it’s important to define chronic cough greater than eight weeks. So many of our patients, I think anybody that really has a cough greater than two weeks automatically feels like they have chronic cough. And most providers may not know the definitions we have for chronic cough versus subacute cough. So number one is making sure that patient truly does have chronic cough. There may be some. Again, because of the influence of the immune system on neural pathways, there may be a subset of patients with any viral illness, especially COVID-19, that have this up regulation that we just don’t know the mechanism of. And so I would always encourage patients that have chronic cough, whether it’s due to COVID or any other viral illness, be assessed by specialist to rule out other causes and then move on to, once those have been ruled out, going on to, again, the treatment of chronic refractory cough.
Speaker 1 (01:03:35)
Thank you so much for that. Dr. Sublett, we’re just going to end with a comment. Someone said, I’m receiving speech therapy for my cough and it’s helping a great deal. I’m still working to improve my raspberry voice, but I’m grateful for this treatment and that leads into what you were saying earlier. So, Dr. Sublett,, thank you so much for joining us today. We totally appreciate all that you had to share. If you could just advance the slide for us, please. At this time, please download the certificate of attendance from your control panel. If you have any difficulties, please email us using the link in your emails. Please join us for our next advances in allergy and asthma webinar as we look at how we can make anaphylaxis less scary for patients. This webinar will be on December 7 at 04:00 p.m.. Eastern. You can register for this webinar on our website at Allergy asthmanetwork.org scroll to the bottom of our homepage to webinars. You can also view our recorded webinars on this page on our website and last slide here. Please visit our website for important guidelines based resources on allergy and asthma. Also, access important medical information on allergies and asthma from our partners, the American College of Allergy, Asthma and Immunology at Allergy and Asthma reliefs.org. Thank you again for joining us today.
Speaker 1 (01:04:56)
Please stay online for two to three minutes to complete the evaluation survey. This is Sally Schoessler for the staff at Allergy and Asthma network. Thank you for joining us for important information on chronic cough, and we look forward to having you join us next time on Advances in Allergy and Asthma. Bye.
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