In addition to today’s resource, here are additional pulmonary guidelines from CHEST:
COUGHManaging Chronic Cough as a Symptom in Children and Management Algorithms | July 2020
Cough is one of the most common presenting symptoms to general practitioners. Read the latest guideline updates on pediatric chronic cough.
ASTHMAManaging Chronic Cough Due to Asthma and NAEB in Adults and Adolescents | July 2020
Learn about the best treatment for cough due to asthma or nonasthmatic eosinophilic bronchitis (NAEB).
Life-Threatening and Non-Life-Threatening Complications Associated With Coughing: A Scoping Review | June 2020
Acute Cough Due to Acute Bronchitis in Immunocompetent Adult Outpatients | May 2020
Chronic Cough Due to Stable Chronic Bronchitis | February 2020
Chronic Cough and Gastroesophageal Reflux in Children | July 2019
Clinically Diagnosing Pertussis-associated Cough in Adults and Children | January 2019
Adult Outpatients With Acute Cough Due to Suspected Pneumonia or Influenza | January 2019
Treatment of Interstitial Lung Disease Associated Cough | October 2018
Chronic Cough Related to Acute Viral Bronchiolitis in Children | August 2018
Treating Cough Due to Non-CF and CF Bronchiectasis With Nonpharmacological Airway Clearance | April 2018
Cough Due to TB and Other Chronic Infections | February 2018
Classification of Cough as a Symptom in Adults and Management Algorithms | January 2018
Pharmacologic and Nonpharmacologic Treatment for Acute Cough Associated With the Common Cold | November 2017
Cough in Ambulatory Immunocompromised Adults | November 2017
Etiologies of Chronic Cough in Pediatric Cohorts | September 2017
Management of Children With Chronic Wet Cough and Protracted Bacterial Bronchitis | April 2017
Use of Management Pathways or Algorithms in Children With Chronic Cough | April 2017
Symptomatic Treatment of Cough Among Adult Patients With Lung Cancer | April 2017
Cough in the Athlete: CHEST Guideline and Expert Panel Report | February 2017
Chronic Cough Due to Gastroesophageal Reflux in Adults | December 2016
Occupational and Environmental Contributions to Chronic Cough in Adults | October 2016
Treatment of Unexplained Chronic Cough | January 2016
Somatic Cough Syndrome and Tic Cough in Adults and Children | July 2015
Assessment of Intervention Fidelity and Recommendations for Researchers Conducting Studies | July 2015
Tools for Assessing Outcomes in Studies of Chronic Cough | March 2015
Anatomy and Neurophysiology of Cough | December 2014
Methodologies for the Development of the Management of Cough | November 2014
Overview of the Management of Cough | October 2014
Today, I review, link to, and embed ACCP CHEST‘s “Refractory Chronic Cough: Disease Overview and Current Management for Pulmonology Specialists”.
All that follows is from the above resource.
Refractory Chronic Cough: Disease Overview and Current Management for Pulmonology SpecialistsApr 8, 2026Transcript
Hello everyone. I’m Anju Peters. I’m a professor of medicine in the division of
allergy and immunology at Northwestern University in Chicago. It is my pleasure today to join my
colleagues Dr. Michael Blae and Dr. Michael Gorriel. We will be speaking on
refractory chronic cough disease overview and current management for pulmonology specialists. Dr. Gorriel.
Thank you Andrew for having me. Uh I’m Michael Gabriel. I am an um board certified palmologist, assistant
professor at Case Western University of Medicine and I’m a medical director of the chronic cough clinic at Cleveland
the clinic. Welcome and Dr. Blaze. Hi Anja. Uh so I’m Dr. Michael Blaze,
allergist immunologist, a clinical professor at the medical college of Georgia at Augusta University in
Augusta, Georgia. Next slide.
So our objectives today are to review mechanisms and pathophysiology underlying refractory chronic cough or
RCC. Increase awareness of RCC as a disease and the impact of RCC across
health, quality of life, social and economic domains. Describe differentiating and clinical
characteristics of RCC and identify challenges that are barriers to a
diagnosis of RCC. We’ll review guideline recommendations and current approaches
to treating RCC in pulmonology settings. Next slide.
So when we think of cough we think of in terms of pathophys pathophysiology
as being involving both central and peripheral nervous system.
The peripheral nervous system initiates the signal the aerant nerve signal to
the uh brain stem. The peripheral nervous system senses the irritation. The signals then travel from the
receptors to the brain stem via the uh vagus nerve. The central nervous system
then translates and modulates the signal. The cough center is specifically in the medula oblangatada and you know
it receives the initial sensory input from the vagus nerve. The motor neurons then transmit the cough to the
respiratory muscles. However, we do know that there can be some higher up cortical modulation and
that the cough can be voluntarily suppressed or even initiated in the
input from the cerebral cortex allows cough to be held or clear the throat
voluntary voluntarily. So, it’s important to note that both peripheral and central nervous system are involved
in cough. Next slide.
So according to the chest guidelines, the definition of cough in adults can be
thought of in terms of duration of cough. Acute cough is cough up to 3 weeks. Subaccute cough is cough from 3
to 8 weeks. And then chronic cough is cough present for 8 weeks or longer. The
duration of the cough is really important because it helps narrow the list of potential diagnosis.
It is important to note that we have guidelines that are evidence-based both in US and outside US and cough should be
managed using these guidelines that are based upon duration of cough.
Next slide. Moving on to chronic cough and Dr. Blae.
Thank you Anja. So let’s talk about chronic cough and specifically we’re
going to look at a great paper that Dr. Peters in fact was the first author that was published last year uh in the annals
of allergy asthma and immunology looking at the diagnostic and management protocol uh for our patients uh with uh
chronic cough. So we can see here to begin with again the diagnosis of chronic cough as Anja mentioned is a
cough in fact that’s been lasting for for greater than eight weeks. So, we want to address red flags and I’ll be
going over in more detail in a minute uh about red flags. Uh but very
importantly, these are conditions where the patient may in fact have a a life-threatening condition that could be
leading to their chronic cough. So, we’re looking for things as mentioned here like fever and chest pain, purulent
sputum, hmoptis. Now very importantly in our initial diagnostic evaluation of
course all these patients uh require a chest X-ray sperometry. One may also
consider the role of exhale nitric oxide levels and then also other diagnostic
tests that again depending upon our history and physical exam that may be of
benefit as far as determining the cause of the patient’s chronic cough. things like a methylcholine challenge, a nasal
endoscopy, uh a sophageal mometry and a sinus imaging. And of course, very
importantly, uh in our history is to look for potential contributors that can
in fact trigger chronic cough. So, is that patient a smoker or uh vaping? Are
they on ACE inhibitors, which we know are a common cause of chronic cough? And
then we look at again underlying conditions uh in different parts of the
body that may in fact lead to chronic cough. Next slide.
So if we look first at uh rhinologic, what we’re looking for primarily here
after our initial evaluation and we again come up with no cause is is upper
airway cough syndrome. So this includes the things such as chronic sinus disease, allergic, non-allergic,
rhinitis conditions. And again, you can see some of the empiric treatments we
may try on these patients. Usually starting with a first generation antihistamine.
Um we may then depending on response go to a topical nasal cortical steroid.
Again, if we think there’s a bacterial infection leading to sinus disease, antibiotics, and again, depending upon
uh how uh how the patient is done with empiric treatments, you may want to go
further as far as evaluations, as you can see here, things like allergy testing and sinus CT scan. If we look at
pulmonary conditions we need to think of uh they include asthma non-asthmatic
eosinaphilic bronchitis again management of these uh would look
at the role of inhaled cortical steroids plus or minus uh long acting uh beta
agonist or bronco dilators and very importantly many times we’ll do a short
trial of systemic cortical steroids if we’re not clear the patient has this condition um and usually that would help
define in fact if we’re dealing with asthma or NAP and again we may want to
do further testing uh as you can see here again all patients should have pulmonary functions but ENO could be
helpful or methylcholine challenge or may need to go as far as a broncoscopy
and then we’re looking at esophageal and again here we’re looking primarily
talking about either gastro esophageal or lurenial feringil reflux conditions.
So we usually uh do anti-reflux measures on these particular patients, avoiding
certain foods, caffeine, alcohol, chocolate, things that can make uh reflux worse. Uh lifestyle changes, not
eating 3 hours before going to bed, raising the head of the bed, uh can be very helpful. And again, starting these
patients uh empirically on proton pump inhibitor is usually twice the recommended dose for at least 8 weeks.
Um depending on response, one may want to try other agents on these patients
and again one may want to refer to GI uh for further evaluation things like
24-hour pH study or impedance studies and then we have neurologic and I guess
we could include here is we’ll talk about refractory chronic cough uh because this going to include patients
with cough hypersensitivity syndrome uh also we have to worry about other neurologic conditions that could be
associated with chronic cough. If a patient in fact has had a stroke, they may be uh impaired and and that could
lead in fact to chronic cough. Uh even chronic cough has been associated with
conditions like Parkinsonism. So again, we might want to try pharmacologic cough
suppression. Um uh respiratory retraining which has to do with use of a
speech language pathologist. And you see here lurenial desensitization. Some of these patients may in fact have
luringial uh hypers sensitivity that may be contributing to cough. These are ones
many times that may go through a superior lingial uh nerve blockage to
try to help uh their chronic cough problem. And again you can see some of the other studies below that could be
used. And then we have systemic diseases and we have no empiric uh therapy here
but things that one may want to think about things like sarcoidosis.
Uh we know that in fact uh one can see chronic cough with with scleraderma
even lupus has been reported uh is associated in fact uh with chronic cough
also uh different malignancies especially lung cancer would be uh included here under these systemic
diseases. So again you can see some of the test whether we talk about corology tissue biopsies etc. So again a very
large differential uh that we need to go through when in fact we’re evaluating
that patient with a chronic cough. Next slide.
So as we go through the workup and again we’re using the uh the US guidelines
that were from the American College of Chest Physicians chest and some of the things that they mentioned that are very
important that we continue to have to look at when we’re evaluating these
patients. So again checking for red flags optimizing therapy for each of
those uh diagnosis. So the things that we had mentioned on the previous slide obviously very important is we need to
uh check compliance in our patients with regularly scheduled and frequent follow-ups uh again to determine in fact
how well the patient is doing and again the patient could in fact have multiple
uh causes of in fact chronic cough. So we need to maintain all the partially effective treatment that we find for
those patients. I think very importantly at every visit is to assess the patient’s uh cough severity. Again,
usually using a visual analog scale is a way of uh uh having the patient uh deter
give us an information related to the severity of their cough uh so that we can follow and see if in fact the
treatments we’re using are having any benefit. There are also validated quality of life instruments. Most of
these are used in clinical studies like the Lester cough questionnaire which
looks at quality of life and symptomatology related to chronic cough. Again, these patients need to have
frequent followup. And again, if one’s not coming to the diagnosis or the patient’s cough is not improving uh with
what we’re doing, then one may in fact want to refer to a a chronic cough uh
clinic. uh they’re founded in many of the the large uh cities throughout the
United States or a specialist uh who in fact has been working in refractory
chronic cough. Next slide. So here we come uh to the red flags that
are listed uh in the chest guidelines. So again, these are things when we’re doing our initial workup of the patient
that as I mentioned before could be associated uh with serious underlying
conditions. So not surprising we would think of hmoptasis under that category
or that patient that’s a smoker that’s got a new cough or a change in cough. um
that uh older adult that has a long packy year history, say 30 pack years or
longer, who’s currently smoking or even has quit in the last 15 years. Again, we’re worried about malignancies.
Prominent disme especially at rest or at night. Could the patient have cardiac problems, congestive heart failure,
horarsseness could be associated uh with malignancy along with systemic symptoms
like fever and weight loss. Is the patient having difficulty when eating or drinking? Are we dealing with an
esophageal malignancy? Are we near dealing with some type of a neurologic condition that may be leading to that
problem? Obviously, chronic vomiting, recurrent pneumonia, and of course, any
patient that we’re evaluating that has an abnormal respiratory exam or an
abnormal chest X-ray. So all of these are red flags that point to us to uh
again look further into these patients for severe problems. Next slide.
So when we talk about a thorough cough assessment uh what’s important here uh
again a a thorough review or prior off uh evaluations. It’s not uncommon before
these patients uh get to us as specialists that in fact they haven’t
been to to numerous uh doctors and have had numerous evaluations before then
including numerous testing and therefore we need to know what those are what uh
and in fact determine in fact uh if in fact we need to do any other types of
testing in the patient. Again, it’s not uncommon for these patients to go through the same test numerous times in
their journey to a diagnosis. Also, we need to know all the medications they’ve tried and what type of benefit uh
they’ve had, whether we’re talking about prescription or over-the-counter treatments. We need to know if they’ve
been on any type of of herbal treatments or supplements for this particular problem and what’s happened. and are
they on any medications that in fact could trigger chronic cough, especially ACE inhibitors. So, we look at things of
the duration of the cough. Again, has it been greater than eight weeks? Again, usually by the time do they get to us as
a specialist, it’s been months or years that they’ve been having the problem. As far as the onset of the cough, is there
anything that the patient remembers and in fact may have triggered the cause of this cough that may give us some hints?
What about the severity of the cough and impact on the patient and their quality of life? Uh the location of the cough.
Does it feel to be more in the lungs or in the throat area or in the sinuses and
drip leading to problems? So this can may help us as far as getting to a diagnosis and the features and
characteristics of the cough. Is it a dry cough? Is it a wet cough? What in fact is the patient coughing up uh if
they are associated with this condition? and what type of triggers have they noted or is there something at work or
is there occupational or other type environmental causes or is it just in the home environment? So all of these
can give us hints as far as the possibility of what in fact is leading to chronic cough uh in this patient
suffering with this condition. Next slide.
So this is a very interesting survey uh that was published in in chest last year
uh and this was a collaboration with chest and GSK. It was a survey of pulmonologists in the United States uh
to really probe to them as far as is their evaluation of patients uh that are
in fact having cough problems. So here we’re seeing is the frequency of probing
cough characteristics and what you’ll notice here this is the percent in fact of the pulmonologist said that they did
probe for these particular characteristics. So you see the highest here being cough history and then
factors triggering cough. Uh very importantly they looked at relationship
to to allergies and asthma. Um, and you’ll see the lowest down here as far
as probing had to do with cough induced dizziness and gagging. And again, as
we’ll hear about refractory chronic cough, it’s not uncommon for some of these patients, in fact, that have
dizziness associated with severe uh burst of cough. the next slide.
If we look further at this survey and look over on the left, we’re looking at the the frequency of uh of probing the
patient history items. So, in other words, as we mentioned before, history is so important and when one is
evaluating these patients uh with chronic cough. So, asking about acid
reflux and upper GI was 96% along with seasonal allergies. So again getting to
upper airway cough syndrome obviously uh the use of of tobacco uh cannabis uh
vaping is also extremely important that family history ACE inhibitors were asked
about 92% of the time uh if we drop down red flags about 85%.
Um so again kind of dropping there but again as we mentioned red flags are extremely important. And then if we look
over on the right, these are less commonly asked. Um, and some of the things I think that are important here,
we see um in the the red boxes. So, sensitivity is to strong smells. Again,
this can be associated uh in some of our patients with refractory chronic cough.
So, you can see how that can be important. I do think we need to be asking the patients about anxiety and
depression associated with their thing. that you see here it’s 39%. And extremely important but only 21% ask
about urinary incontinence and it’s just been my uh seen in clinic is that uh
patients don’t volunteer that in fact uh their severe coughing is causing urinary
incontinent. So I think unless you specifically ask uh you’re not going to get that history of stress urinary
incontinence. Next slide. So let’s move on and talk about uh
refractory chronic cough. So what do we mean by refractory chronic cough?
So in fact it’s a subset of patients with chronic cough. I think we still don’t have the exact uh percentage but
we know that there is a definite percentage of these patients that have chronic cough uh that would fall under
this definition. So how do we define this? These are patients that again have
chronic cough. So, it’s been going on for greater than eight weeks. one goes through guidelined directed uh therapy
uh and a thorough evaluation as we’ve talked about again including uh the red
flags and then looking for what we call the big three the most common causes of
chronic cough in the patient population and that being pulmonary and we group
together asthma non-asthmatic eosinaphilic bronchitis gastro esophageal reflux disease and
then upper airway cough syndrome as we mentioned And so all of that in fact has been ruled out because basically this is
a diagnosis of exclusion. We do not have a biioarker at this time that will tell
us specifically that the patient has refractory chronic cough. What we do know is that this is a much more common
condition in the female population. The male it’s about 2:1 uh two u as far as
about 2/3 of women. Uh it’s about 2/3 women 1/3 men. when we look at the
numbers and the highest incidents we see are in the patient population here uh in
their 50s and 60s. Next slide.
So here are some of the other things again and we’ve mentioned some of these already that again we all need to look
at as far as evaluation before we make that diagnosis of refractory chronic
cough in that patient. So we mentioned again asthma cough ovarian asthma would
be included in that non-asthmatic asynth bronchitis obviously uh COPD which we uh
could diagnose from the history and spometry um gird as we mentioned chronic
rhinoitis which is part of the upper airway cough syndrome uh bronchiacttois
interstitial lung disease including we’d mentioned before sarcoidosis and then inducible lingial obstruction ruction
vocal cord dysfunction. So all of these again we need to rule out before we give
that patient that diagnosis of RCC. Next slide.
Probably the most disturbing thing associated with refractory chronic cough
is that patients long journey to diagnosis of the condition. And I think
one of the real problems here that we have to deal with is in fact lack of awareness that in fact cough here is not
a symptom but cough here in fact is a true disease and it’s distinct
refractory chronic cough from the typical chronic cough uh that we talk
about and I think one of the problems we have here um uh is that in fact there’s
this inconsistent terminology there really is a push now that again We describe these patients under the term
refractory chronic cough, but unfortunately, as we’ll see shortly, many other terms have been used out
there. So, we’re not talking the same language. One of the things we commonly see that happen to these patients is
referral to numerous specialists and there’s really not a good cor coordination of care for these patients.
In fact, we know that these patients in fact uh tend to have many visits to different specialists. this one study
out of Spain, 14 visits uh due to chronic cough over a three-year period.
Uh and another study done in the US that 68% of pulmonologists survey their
patients with chronic cough had already seen uh two or more health care professionals for uh for evaluation. And
if you do the same type of survey and patients that go to chronic cough clinics, you find out that they’ve seen
many more patients, many more physicians for this evaluation.
with all these numerous visits uh to different physicians, they get a lot of
redundant tests. They get a lot of numerous trials of therapy, in many cases the same therapy over and over
again. And again, the studies clearly show that the vast majority and this
particular survey showed 93% reported limited or no efficacy uh uh of the
treatment. And uh in another survey that was done of health care professionals, in fact,
they didn’t realize that there were specialist specialized cough centers uh that are throughout the United States
that can diagnose and treat chronic cough. So unfortunately uh so many physicians do not know that there are
these special areas where these patients can be sent uh for really a multidisciplinary approach as far as
work up and management. And the other problem is the patients get frustrated.
Uh they get tired of seeing one doctor after the other and they learn that they
just really have to live with this and in fact they’re just lost to followup. Many times they go to uh complimentary
or alternative uh care types of treatment. Um but we lose so many of
these patients because of that. So we have to do a better job uh as far as
getting quickly to the diagnosis of RCC uh so that these patients can get proper
management and treatment. So with that I’m going to turn it over to to Dr. um
to Dr. uh Gabario uh to again go over more about refractory chronic cough.
Thank you Michael so much. um quite a journey and when we see these patients in clinic um we we can understand their
their frustration and and and their confusion and this confusion really comes first from the lack of um
diagnosis. So they say why are we coughing? And when uh um recently 700 um
healthcare providers were surveyed they they used completely different terminologies trying to describe the
same exact um process or trying to describe the same exact cause of cough. It’s either
idiopathic chronic cough, persistent chronic cough, refractory chronic cough and exclined chronic cough. And then the
list continues to go over 15 different terms to describe just one process
happening to these patients. Um Cves that has been ongoing for long time and
has been refractory to um guide guideline direct treatment and they
haven’t really received a test u or or or or or any um validation for for their
symptoms or any relief of their symptoms. So logenic cough, habitual cough, psychoggenic coughs, they have
been labeled with so many different um terminologies. And next slide when we
look at what pulmonologists commonly have used to to to report back on the
recent survey that was done last year in collaboration between chest and GSK looking at pulmonologists. We would like
to use chronic cough or um neurogenic chronic cough or refractory chronic
cough. We also come up with our own list of um names for for for for this um an
anxiety related cough um cough hyper sensitive syndrome just to make it look
a little bit more fancy and this was looking at more than 400 pulmonologists trying to describe uh how do they
diagnose this patient population. Next slide please.
And when we look at the characteristics of these patients coming with refractory chronic cough, we can understand that
they p they present with a dry or a minimally productive um cough that has
been going on for more than 8 weeks, but typically it’s been going on for a month or even years. They report this coughing
burst or bouts or fits that can last between several seconds to several minutes. And some of these bursts can be
consequential in regards of um vomiting or um significant dizziness even
sometimes passing out and some patients have passed out while driving and caused uh them to be involved in in in motor
vehicle accident. Uh cough hyper sensitivity has been observed upon exposure to different triggers and
patients would report to you that they have been coughing more if they are laughing or talking or singing. uh they
get in the car or when they walk outside and the get exposed to to cold air they
start coughing. If they get exposed to certain aerosols or scents or perfumes
they would start coughing. They report often times to a tickling in their throat or some discomfort that urges
them to cough and this can lead us to how um neuronal hypersensitivity could
be contributing to the development and persistence of refractory chronic cough. Next slide please.
These patients are um in addition to the confusion that they have been dealing
with, they have been depressed, they have been anxious uh as well because of lack of diagnosis, lack of uh um
validation for their symptoms despite significant uh workup, repeated testing,
repeated treatment trials seeing different providers and up to more than quarter of these patients have reported
anxiety or depression feelings. It happens to be um more common in in women
as we have seen and twothirds of these women have reported urine incontinence. Um by itself this is a problem. It’s
very under reportported problem. We don’t ask patients as we are supposed to to ask them in the survey. It was only
asked about 20% of the time. But more impactful that these urine symptoms
would not be um successful to to be treated by urologist. uh patients have
failed treatment before and their urologists have uh advised them to get treatment and evaluation of chronic
cough before they would consider retreating them. uh in the postcoid era
about 18% of patients with postcoid have report have been reporting refractory chronic cough and in a recent survey in
Spain um looking at more than 120 patients over a year period more than
2/3 of these patients have reported that the chronic cough has significant impact
on their quality of life quite a bit much or very much impact on their quality of life which is what we see in
clinical practice and how patients are reporting their symptoms to be impactful to their quality of life. Next slide
please. As a as a group of um community of palmologists, how can we do our best to
reduce the time to refractory chronic cough diagnosis? And in the next slides, we will try to dive a little deeper into
understanding the development of refractory chronic cough. And to piggyback on what we have heard before,
refractory chronic cough happens primarily because of um disregulation in the peripheral as well as the central
nervous system where the peripheral nervous system has been or has become more hyper sensitive and the central
nervous system that poses the power to inhibit and regulate cough has become
more complacent with de with with the persistence of this refractory chronic cough. [sighs and gasps]
Next slide please. We have been able to identify different
receptors in the airway that can be triggered and um provokes uh patients to
to cough and depending on the trigger these uh receptors would be activated
and successfully enough. There is promise that some of these receptors if we can inhibit them we can help patients
feel better. In regards to this um refractory chronica, there has been um
more emphasis on the P2X3 receptors, TRP, V1 and uh A1 receptors and A
receptors. Uh there is work on the sodium uh receptors that has been going on. But we also understand that in the
airways of patients with refractory chronic CS there is significant increase in peripheral nerve branching and
density that causes the airway to become hyper innervated and hence hyper sensitive. And when we look at MRI uh
results or MRI studies of the central nervous system in patients with um refractory chronic cough as compared to
healthy control, we could see that there is structural and functional changes in the prefrontal cortex and midbrain
explains why this uh set of patients are having difficulty
uh with refractory chronic cough at the peripheral nervous system as well as the central nervous system uh pathways.
Next slide please. In order to help reduce the time to
diagnose the refractory chronic cough, as we understood earlier, it’s diagnosed of exclusion. It’s important to
understand and label correctly the symptoms of patients coming with this refractory chronic cough. And here are
few symptoms that we can easily identify in in in clinical practice when we are seeing these patients in clinic. Alotia
for example would be a cough triggered by non-tussive stimuli things that normally should not cause you to cough.
Talking, laughing, taking a deep breath, um uh eating or um drinking cold fluids
would be uh uh triggering to cough. This would be called aloasia. Hypertia is
exaggerated cough response to tus stimuli that normally would cause mild or infrequent cough. And for example uh
smelling strong smells exposure to fog or rain or smoke or neibilized
irritants. Laria parakeesia is an abnormal sensation in the throat that precedes or provoke cough reflecting
sensory nerve hyperexitability. People patients would common report feeling um
itch or a dry patch or a feather feeling or a sand feeling or burning tingling
and they would um commonly report it as tickling in my throat. And then there is
a throat clearing compulsion where patients are constantly telling us where we have this uh throat clearing feeling
when nothing it it feels like I have mucus in the back of my throat and I try to constantly try to clear it up and
it’s nothing is coming out. And last is urge to cough patients with a strong premonetary sensation that a cough is
eminent or about to occur and they can’t really uh suppress it or or or control
it. uh all these uh symptoms are reflective of what we call neuronal hypers
sensitivity in these patients. Next I will leave I will leave it to Dr. Peters to wrap it up.
Thank you very much. What we also know is pulmonologists do not always probe for symptoms suggesting neuronal
neuronal hypersensitivity. Some of the symptoms of neuronal hypersensitivity as mentioned earlier
are the tickling or irritating sensation or feeling of rawness in the fairings
and larynx area resulting in an urge to cough allotysia and hypertysia. Dr.
Gorrielle mentioned earlier and so really do you probe to see if your patients is experiencing a global s
globus sensation or not? In the cough clinic, we tend to probe it much more.
Those of us who deal with a chronic cough quite a bit. And triggers that suggest a neuronal hypersensitivity
include things that you know we see on a daily basis and most people don’t cough
with these but patients with neuronal hypersensitivity in RCC often do.
sensation of dryness, cold temperature, smells, smoke, eating or drinking, even
talking or laughing, and even lying down. Next slide.
So, it’s important to consider neuronal hypersensitivity early in the patient journey in patients you’ve diagnosed
with refractory chronic cough. At what point did you begin to consider that neuronal hypersensitivity may be the
underlying factor in the patient’s cough? And as you can see in the cough clinic, um
it mentioned to others only at the very end after having ruled out everything I
can think of and exhausting all consults with other specialist it was 31%
and in others it was 48%. It’s important to also note that in the
cough clinic, it was considered during the rule process as a common underlying ideology are being eliminated from
consideration. What this really tells us is that increasing awareness of neuronal
hypersensitivity and associated symptoms could lead to earlier consideration and
diagnosis of RCC which of course would improve the patient journey and
potentially outcomes. Next slide.
You know, another non-farmacologic um therapy that has shown to decrease
cough frequency and it’s something we can use with pharmacologic therapy is speech and language therapy. What this
entails is education of our patients. In addition, strategies to control
cough, improve vocal hygiene, and even psychoeducational counseling as part of
speech and language therapy. The goal is to reduce the lingial irritation that
often underlies RCC, increase the voluntary control over
coughing, interrupt or prevent coughing episodes and to address associated
symptoms that these patients suffer prompt including dysphonia and the increased lingial sensitivity.
The different interventions with speech and language therapy include cough suppression techniques. For example,
swallowing and breathing strategies are taught. Vocal ed hygiene education with
nasal breathing and then avoiding triggers such as caffeine and alcohol that worsen refractory chronic cough. An
important psycho education to help patients deal with and control their chronic cough.
The results in refractory chronic cough as I mentioned earlier show benefit decrease in cough frequency but we need
more research in this area. Next slide.
There are quite a few emerging options for refractory chronic cough. One of the main ones is P2X3 receptor antagonist.
These block the receptors triggered by ATP on the veagal aphrine nerves and
then that leads to neuronal hypersensitivity. These are not FDA approved in the US but
are approved elsewhere and studies are ongoing including in US.
Opioid analesics have shown benefit but are limit limited due to side effects.
However, the mixed agnus and tagnus these activate the kappa opioid receptor
while simultaneously blocking the muopioid receptors. So they limit the side effects but show us the benefits.
These in phase two studies have shown benefit in chronic cough associated with
IPF and also in early studies have shown benefit in refractory chronic cough. The
best part is you lower the risk of adverse effects including lowering risk of dependence and sedation.
Others that are being studied and have shown benefit in early trials including neurocinine receptor antagonists which
block substance P mediated cough pathways and also sodium channel
blockers that can then prevent or stop nerve signals in the aerin nerve that
can then trigger the cough reflex. Again these are all in early studies. They
have shown some benefit in small uh number of uh clinical trials with
with small number of patients. Next slide.
So refractory chronic cough. Key takeaways chronic cough is cough that lasts greater than 8 weeks. It’s
associated with varied ideologies as was discussed earlier. It’s important to identify specially identify early and we
as specialists should identify these early and treat the underlying issues.
Refractory chronic cough or RCC is a disease not a symptom that occurs in a
subset of chronic cough patients. It impacts quality of life significantly. As was mentioned earlier, it lasts for 8
weeks or longer despite treatment of underlying conditions in guideline treated directed care. It is a diagnosis
of exclusion and neuronal hypers sensitivity we think drives RCC.
So that with this I want to thank my colleagues Michael Gorriel, Michael Blaze and thank you for joining us.
These are some of the references that were utilized in this presentation. Thank you.
