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A Pulmonologist on Chronic Cough
Conversations in Chronic Cough: A Pulmonologist’s Perspective

Released: September 09, 2025

Peter Dicpinigaitis
Peter Dicpinigaitis, MD
Activity Information

Activity

Listen as pulmonologist Peter Dicpinigaitis discusses his approach to the diagnosis and management of patients with refractory chronic cough in the context of a clinically relevant case and provides insights regarding emerging therapies.

This transcript was automatically generated from the audio recording and may contain inaccuracies, including errors or typographical mistakes.

In terms of chronic cough, why do not we begin with a representative case, and then that will get us started.

This case involves a patient named Joan, who's a 51-year-old woman presenting with a cough of four years duration. When asked, it started with an upper respiratory tract infection. That is what you should always ask your chronic cough patients. When asked, she said, it did start with what seemed like a typical cold, the one I get usually every year that lasts five or six days. But on this particular occasion, the cold symptoms went away after five or six days, but this dry, persistent cough has been with me every day since.

Not only has it been with the patient every day, lately, it has gotten worse and the bouts have been more severe. Her primary care physician tried a variety of over-the-counter cough medications and also prescription benzonatate, which did not help.

She had a normal chest x rays done two years ago in the middle of this chronic cough episode. She is otherwise in good health. No recent weight loss.

The cough is, as typical, it is dry. It is throughout the day. She tends to sleep okay at night without interruption, and she frequently has a tickle sensation in her throat, not only before a cough episode, but even in between cough episodes, which sometimes is as bothersome as the cough itself. The cough is triggered by things that do not make other folks cough like mild odors, laughing, singing, talking.

When these episodes become quite severe, as they have in her case, she then has episodes of cough-induced stress urinary incontinence, which actually is very, very common. In fact, we did a study at our cough center showing that 62% of women suffering from chronic cough have episodes of stress urinary incontinence. They typically will not offer this history unless specifically asked.

As one can imagine, these patients then are afraid to go out in public for fear of having one of these episodes and having either an episode of urine incontinence, or just simply drawing attention to themselves when they are coughing, especially nowadays.

Also since the cough has, up until now, gone undiagnosed, she still does not know whether this cough may not be underlying some serious illness that she has not yet been told of.

As I said, her past medical history is pretty unremarkable. A lifetime non-smoker, she is not an ACE inhibitor medications. She has been an accountant for 25 years, so therefore she has no significant occupational history.

Physical exam was fairly unremarkable. She had some mildly swollen turbinates on nasal exam, maybe some slight posterior pharyngeal erythema with some cobblestoning. Her lungs were completely clear, and the physical exam otherwise was unremarkable.

When she was being treated by other physicians, she did get treated for asthma because along the way during this four-year odyssey, she had a positive methacholine test. She was treated for asthma without success and other conditions, according to her previous physicians were ruled out, and therefore, she had been given a diagnosis of refractory chronic cough.

We will leave refractory chronic cough at this point and continue our discussion of chronic cough and get back to making sure we make the appropriate and correct diagnosis of refractory chronic cough.

Definitions

Definitions are always important. Chronic cough simply means you have had a cough for more than eight weeks. It is agnostic of the etiology. If you have had a cough more than eight weeks, you have a chronic cough. It is quite common anywhere from 8% to 12% of people describe having had a chronic cough in the previous year on multiple surveys, especially in cough centers like the one I run, about two thirds of patients presenting are women because women have a more sensitive cough reflex.

Chronic cough patients come in all ages and sizes, but the peak ages are in the 50s and 60s. As I said, women predominate about two thirds. The majority of patients that come to cough centers are in fact lifetime non-smokers.

As physicians meeting a patient with chronic cough, our job is not to give the patient a cough suppressant. But we need to perform a very thorough evaluation to find out if we can identify an underlying cause of that chronic cough, treat the underlying cause, and make the cough go away. Only if we are unsuccessful in finding a treatable underlying cause, only then would we go on to then actually suppress the cough.

Initially with history, of course, we talk about the length of time of cough, the nature of the cough, is there a history of smoking or taking ACE inhibitors? Obviously what previous tests and treatments have been done by other physicians?

The American College of Chest Physicians has published guidelines and they make it a point to remind us that as we are beginning the evaluation of a patient of chronic cough, make sure to identify what they call red flags, meaning problems that need immediate attention before you go forward with the evaluation of a chronic cough. Those things are obviously serious things like if the patient describes hemoptysis, or if it is a smoker with a change in the nature of the cough or new hoarseness, if there is shortness of breath associated with the cough, fever associated with the cough, weight loss, peripheral edema, difficulty swallowing, recurrent pneumonias, vomiting.

These things obviously need immediate attention before we go ahead and then continue the workup for the chronic cough.

The paradigm that we, as pulmonologists, have been following for decades now is the following. That is, if you have an adult patient with chronic cough who is not a smoker, who is not on an ACE inhibitor medication, and whose x ray does not show any active disease that might explain the cough, then it is most likely that that cough is due to one or more of three main things.

Some people call it the big four. I call it the big three because I lump two of them, and those big three are as follows. What we now call upper airway cough syndrome, that historically or in layman's terms, was post-nasal drip syndrome.

Then basket number two is the eosinophilic airway inflammation disorders, which include not just asthma but an entity of non-asthmatic eosinophilic bronchitis.

Then basket number three is gastroesophageal reflux, or GERD. I could spend a 45-minute program just talking about how we work up these three things to exclude them in a patient with chronic cough, but suffice it to say that we have to work very hard to evaluate if these conditions are present, and then treat them with the appropriate medicines at the appropriate doses for the appropriate duration of time before we rule out that the cough is due to one of these things.

For upper airway cough syndrome, sometimes inhaled steroids or inhaled antihistamines may help. I very frequently use an oral first-generation antihistamine because I find these drugs particularly effective for asthma, and non-asthmatic EB. It may, in the beginning be appropriate to begin with inhaled steroids. I am seeing patients in my cough center who have been coughing for years and decades, so I have a very low threshold to give a short course of oral prednisone just to confirm that this cough is steroid responsive or not.

For reflux, aggressive anti-acid reflux therapy might include a twice-daily proton pump inhibitor half an hour before breakfast, half an hour before dinner, and lifestyle measures including sleeping on two or three pillows. Do not eat for two hours before bedtime and avoid foods and drinks that exacerbate reflux, which are caffeine, alcohol, spicy foods, chocolate, peppermints very acid foods like tomato sauce. It is important to discuss those with the patient.

If we, in fact, have gone through that exhaustive exclusion of these treatable causes of cough, then and only then can we make the diagnosis of refractory chronic cough. Again, the diagnosis or the definition of RCC is a chronic cough that has not responded to appropriate treatment trials against the known common causes of chronic cough.

What is next? Joan has now met the criteria of having a refractory chronic cough because she has been appropriately treated for all of the known underlying treatable causes of chronic cough, with the right medications at the right doses for the right duration.

Now we rather not get to a diagnosis of refractory chronic cough because we do not have good options for it at the moment, but what we do have is the following. When we are faced with the patient with refractory chronic cough, we often use what we call the neuromodulator drugs, which include amitriptyline and old tricyclic antidepressants, and gabapentin or pregabalin.

In my experience, these medications work only in a minority of patients. Oftentimes, especially with gabapentin, they are not well tolerated in terms of sedation.

Speech and language pathologists can be very useful to assist in the patient with refractory chronic cough. However, there are very few SLPs that are in fact interested in and expert in chronic cough, and we definitely need more of them. And low dose morphine has been shown in one randomized controlled trial as being effective. But of course there are issues with chronic therapy with opioids.

At this point if those options are exhausted, there may be referral to another specialist. If you live in a place where there is a chronic cough center available, then that would be something to consider.

Now why do some of these patients have refractory chronic cough? In the last decade or so, we have understood that the reason underlying this diagnosis is a hypersensitive cough reflex. We termed that back in 2014 with our first publications deducing the concept of cough hypersensitivity syndrome, where these subjects cough from triggers that do not make other people cough.

Oftentimes, they will be very similar in presentation. They say that, they have an urge to cough, not just the tickle in the throat, but a sensation of a glob of mucus in their throat, a globus sensation, very common among these patients.

They will often tell you that talking, laughing, singing will induce cough, cold air, or change of air temperature, cold to warm, warm to cold, dry air, strong smells will induce cough because of this hypersensitized cough reflex.

Thankfully, we have learned a lot about the underlying mechanism of cough in the last decade or so, and learning about what receptors and ion channels are important in the pathological cough reflex has allowed us to identify antagonists, and in some cases, agonists to those receptors to find medications that may be effective for cough.

Thankfully, the last decade or so has been very, very active in terms of us discovering or currently having in the pipeline seven or eight programs looking at drugs that may be effective cough drugs that hopefully will be medications that we can use.

The furthest along are the P2X3 antagonists, and one of them named gefapixant, has actually already completed phase III trials, and gefapixant has been approved for use for refractory chronic cough in Europe and Japan. Unfortunately, the United States FDA has on two occasions declined to approve this medication, and we probably would not have it.

However, another P2X3 antagonist named camlipixant is currently completing phase III trials, and the hope is that those studies will read out in 2026, and perhaps we will have the drug approved in 2026 or not long after. This is another P2X3 antagonist.

Now there is some other molecules being looked at that are very interesting that are little earlier on. There is several phase II programs going on. One is a drug called taplucainium, which is a sodium channel blocker which is an inhaled agent. There is a TRPM8 agonist, which is a menthol type molecule being looked at. There is a neurokinin antagonist being looked at, and NMDA antagonist.

Also very interesting opioid type drug that in fact is a mu opioid antagonist. The opioids with which we are familiar, morphine, codeine, hydrocodone are mu opioid agonists. But nalmefene is in fact a mu opioid antagonist, but a kappa opioid agonist. It is through the kappa agonism that the drug achieves its antitussive effect. In fact, just recently read out a positive phase II study.

To summarize, definitions are important. Remember, chronic cough simply means a cough that has been present for more than eight weeks. However, if we thoroughly evaluate and treat all of the known underlying causes of chronic cough and that chronic cough persists, then it is appropriate to make the diagnosis of refractory chronic cough. We do not have great options at this point for RCC, but we hope that some of the drugs about which I spoke a minute ago will become available to us, and we need to be very aware of RCC as a definition, because most of the drugs that I have discussed are going to be labeled for refractory chronic cough.

Refractory chronic cough can have a tremendous impact on patients’ lives. We did a study showing that more than 50% of patients coming to see us tested positive on a clinical depression scale. These people become shut ins. They do not go out socially. It is not uncommon for me to see a patient who has not been to a movie or restaurant or to church in 10 or 20 years for fear of a cough paroxysm drawing attention to themselves.

Hopefully, these pipeline drugs will be available to us to help. It has been an exciting few years in the cough space. We need to make sure we treat chronic cough appropriately. Let us only get to refractory chronic cough correctly. Let us not skip any potentially treatable causes. Hopefully in the next year or a few years, we will have some new drugs available to treat refractory chronic cough.