Understanding Chronic Cough and Cough Hypersensitivity Syndrome with Professors James Hull and Surinder Birring

In this episode of BLA Connections: A Clear Voice, host Natalie Watson speaks with Professors James Hull and Surinder Birring, leading experts in respiratory medicine, to discuss the challenges of diagnosing and treating chronic cough.

Chronic cough, affecting 5-10% of the population (primarily women), is a debilitating condition often misdiagnosed and misunderstood. It can significantly impact quality of life with symptoms such as urinary incontinence, throat irritation, and headaches.

Professors Hull and Birring explain how chronic cough is now recognised as a neurological condition linked to nerve hypersensitivity, moving away from being seen as just a symptom of asthma, reflux, or nasal disease. Questions explored and answered in this episode cover why chronic cough is frequently misdiagnosed. How is cough hypersensitivity syndrome changing the approach to treatment? and what are the latest advancements in therapies, including new treatments like Gefapixant, that offer hope for managing nerve sensitivity and improving patient outcomes?

Top three takeaways:

• Chronic cough is common and frequently misdiagnosed, leading to a cycle of treatments for conditions like asthma, reflux, or nasal disease, which may not be the root cause.
• Cough hypersensitivity syndrome reframes chronic cough as a neurological condition, prompting a shift in treatment focus.
• Promising treatments, such as Gefapixant, aim to address nerve sensitivity, offering new hope for chronic cough sufferers.

We hope you enjoy this episode.

Resource Links

ISSC Hull Airway Reflux Questionnaire: https://www.issc.info/HullCoughHypersensitivityQuestionnaire.html

Article:  Development of a symptom-specific health status measure for patients with chronic cough: Leicester Cough Questionnaire (LCQ)
https://pmc.ncbi.nlm.nih.gov/articles/PMC1746649/pdf/v058p00339.pdf

Article: Development and validation of the Newcastle laryngeal hypersensitivity questionnaire

https://pmc.ncbi.nlm.nih.gov/articles/PMC3931290/

Contact Information
Visit www.britishlaryngological.org and our podcast library.

Cutting Edge Laryngology 2026 registration is now open: Register here

Email: enquiries@britishlaryngological.org for any questions or topic suggestions you may have for future episodes.

This show is brought to you by the BLA; you can follow us on  X, Linkedin and Instagram hosted by Natalie Watson @surgeonsinger, produced  and directed by Heather Pownall of Heather's Media Hub Ltd and award-winning producer. 

The opinions of our host and guests are their own; The BLA does not endorse any individual viewpoints, given products or companies. 
If you enjoyed this podcast, please rate, review and subscribe with the podcast provider of your choice.

Transcript

Host: Natalie Watson

Welcome to BLA Connections: A Clear Voice. I'm your host Natalie Watson, and I'm delighted to bring you discussions and insights from experts from across the globe on all things laryngology.

Today we have a very special podcast, with two world renowned respiratory physicians specialising in cough. First, may I introduce Professor James Hull, a Consultant Respiratory Physician at the Royal Brompton Hospital in London, and Professor Surinder Birring Consultant Respiratory Physician at King's College Hospital, both of which I have the huge pleasure of working with as part of the King's Health Partners in our unified cough service. And last season, I promised you in this podcast, that after interviewing Professor Ahmed Geneid from Finland, I said that we would be talking from the physician point of view. So here we are. We have this very special physician podcast.

Speaking of which, the surgical podcast, you can listen to that podcast in Series Five: Exploring Chronic Cough. So as a direct comparison, I'm going to keep the format and questions the same, so we can really see the difference, or not, from a surgical and medical approach to the management of chronic cough. Thank you both for joining us today.

Professor James Hull

Thanks, Natalie.

Professor Surinder Birring

Thanks Natalie, thanks for having us, and it's great to be here.

Host: Natalie Watson

Brilliant. It's a pleasure to have you both on the podcast today. Chronic cough, Surinder, tell me about it? One of the persistent throat symptoms that we see, certainly in the laryngology clinic, but also in the respiratory clinic.

Professor Surinder Birring

Cough is important. It's the most common reason why we consult our general practitioner, and that's an acute cough, due to a viral upper respiratory tract infection. But chronic cough is also common and important. A common reason to see a GP, and is one of the most common referrals to respiratory and ENT outpatient clinics, and allergy too.

Now, epidemiological studies estimate population prevalence of around 5% to 10%, so it's an extremely common condition. It does affect females more than males, but it can affect anybody. Now the reason why patients go and see their doctor is because a cough is so impactful, it can affect any part of their life. It causes physical symptoms such as retching, headaches, pain, but stress urinary incontinence is extremely common because it's a female predominant disorder. Up to 60% of women affected with chronic cough experience urinary incontinence, and it's often a hidden symptom. Now a cough is a very challenging condition to assess and diagnose, and the consequence of that is the patients suffer a vicious cycle of investigations, treatments and multiple consultations, because they often can't find the answer to their problem. So it's a really challenging condition to manage.

Host: Natalie Watson

It is indeed, and I'm really pleased that you brought the urinary symptoms up, because that really is unseen. And actually having good links with your pelvic floor, physios, and GU and guided teams is really important, from a laryngology, and respiratory, and allergy position.

Professor Surinder Birring

Absolutely, we frequently forget to ask. Most patients don't volunteer this symptom and it really affects them, and is probably what's driving their consultation. So it's an important problem to address, and a good way of establishing the severity of urine incontinence due to cough, is to ask the patient if they're having to wear pads and the frequency of changing the pads to assess the severity of the problem, and then putting them in touch with the women's health physiotherapist and uro-gynae services.

Host: Natalie Watson

Yeah. So Jim, what are the common causes of chronic cough?

Professor James Hull

Well, Natalie, when we see people who've been coughing for more than eight weeks, it is of course, important to rule out anything that's in the lung. Most people should have some form of imaging. And obviously, for most people, that looks like a chest X ray. More commonly now, people are getting access to CT scans. It's important to rule out a structural problem in the lung. And there are some other important first line things to think about. For instance, of course, the use of ACE inhibitors, which are associated with coughing. And even this week, I saw a patient who'd been coughing for about 18 months, looked through the drug list, and there was an ACE inhibitor. And the patient said, “Look, yes, the cough started a few weeks after starting the ACE inhibitor”. But generally after that, most patients, I find, go on a bit of a sort of a wild goose chase, but they go round and round a cycle of three main diagnoses, either nasal disease or something dripping onto the back of their throat, which I'd love to chat to you about, a diagnosis of asthma or an asthma related issue. So most people have had a trial of the blue inhaler to see if it helps their cough. Or finally, reflux, and most people get given a PPI to try and see if that helps their cough. And I'm sure we can touch on the sort of thought processes we have about these different treatments, but often it is very frustrating for patients, because they go around that cycle and then they go right back to the start again to try and treat these conditions.

And yet, for myself and Surinder, and many in the world of cough now, we recognise that cough is actually probably, for many patients who have had it for weeks to months, more like a neurological condition where the nerve fibres are irritated. And so it's a bit like migraine, where people go off and they have tests of their vision, they might have scans of their neck or their head, but ultimately, there's something wrong with the nerve fibres. And so treatment targeting the nerve fibres helps people with migraine. And we find the same in our cough clinic. I'm sure you do in your ENT service?

Host: Natalie Watson

Yeah. I mean, what would be fantastic is if we could somehow measure the hypersensitivity, or the sensitivity of the nerve endings, on the mucosa. That would be the ultimate investigation. Because generally, when you look at people with chronic cough from a flexible nasopharyngoscopy, nasal laryngoscopy point of view, apart from if you see something glaringly obvious, like a polyp or something or granuloma where they've been coughing all the time, there really isn't much to see unless huge amounts of irritation.

Professor James Hull

Yeah, and it's one of the, I'm sure, very irritating things for patients, in that, they have this horrible symptom. Surinder outlined at the start, the impact it has on quality of life and other aspects of people's life, and yet they repeatedly go through either diagnostic tests or treatment trials where people say, we haven't found anything, there's nothing to see, be reassured by that.  And it isn't very reassuring when you've got a symptom which continues to plague your life, and we do need better tests. Surinder might be better placed than me to talk about some of the sensitivity tests that are available and their limitations, but people have tried to look at sensitivity of the nerve fibres in different ways.

Professor Surinder Birring

Yes, we can measure the sensitivity of the cough reflex in the laboratory. And this is most commonly tested by asking patients to inhale capsaicin, which is an extract of chilli pepper, a very potent cough provoking agent, and that determines the sensitivity of the reflex. The test does have limitations in that it's not practical for routine clinical use. It takes time setting up, and probably more importantly, there's a lot of overlap between healthy people who don't cough, and people with the disease. Whilst as a group, cough patients are much more sensitive to capsaicin, so are some healthy people who said discriminative ability is probably not as much as we would like, for it to be a disorder, a test to identify this upper airway or laryngeal sensitivity.

So we're left with diagnosing this condition mainly on the symptom profile, which I'm sure Jim and I can easily recognise when these people walk in through our clinic door. They tend to be patients who describe an irritation in their throat, often a tickle, or an itch, or a scratch, or it’s an urge to cough. And that's actually the primary symptom of this disorder, this neuropathy disorder.

Jim was alluding to, they'll often have multiple triggers of cough, such as strong smells, perfume, smoke, but often triggers that you don't expect to cause cough, such as talking and eating. And so a combination of these symptoms is a largely dry cough and the predominance of female middle aged patients, one does start to build a picture of somebody with a hypersensitivity disorder. And European respiratory society a few years ago, did coin a definition of a condition called cough hypersensitivity syndrome, to move away from cough being merely a symptom of other diseases, and actually being a primary disorder in it’s own right, a disorder of the sensations.

Host: Natalie Watson

Yeah. And there's also some other tools we use, for example, questionnaires, to try and help with the diagnosis, and some of which you've both been very instrumental in creating. So would you like to talk through that? And we can put some links in the show notes.

Professor Surinder Birring

Yeah, I could address that, in that there are questionnaires available, such as the cough hypersensitivity questionnaire we are currently developing, or the larynx that is a new Newcastle hypersensitivity tool. They assess triggers and sensations associated with the chronic cough. And there's another tool, the Hull, airway, reflux questionnaire. Their ability to diagnose the condition is yet to be established. So I think, for the time being, they're useful tools to administer the patient pre clinic, either in the waiting room, or electronically, prior to their appointment, because it's a limited time we have in a consultation, and it's difficult to go through so many triggers and trait sensations. So I think they're very useful in that sense, but we haven't got to the point where we know their ability to diagnose, and know the thresholds for these questionnaires to diagnose, but they're useful to assist the consultation.

Host: Natalie Watson

Yeah. So you both sit in tertiary centres with big cough clinics. What's your approach for the work up of cough in your scenario?

Professor James Hull

Very interesting. Listeners might be interested to look at a recent Delphi process in this area, where several centres from right across the world, and clinicians who work in those centres, were asked to rank and discuss the type of workup and investigation they think is appropriate. And there is a degree of disagreement. And when I go and chat to European doctors, for instance, there is this feeling that really every cause must be excluded. And that does take in a very extensive workup, which often in many European centres, includes a bronchoscopy, to look and lavage the lower parts of the airway and to make sure there's nothing sitting inside the airway. And that would also include CT scans and often tests such as broncho provocation tests to look for asthma.

I think myself, and Surinder, and certainly the UK practices, is a little bit more, let's say, pragmatic in terms of our ability to access these sorts of tests and also to try and speed people through a diagnostic pathway. And often (and Surinder has written some very nice reviews and editorials on this area), these tests may be positive, but they may not necessarily directly give you a cause of that cough. There may just be simple bystanders to the hypersensitivity process, and therefore their utility is somewhat limited, but generally speaking, for me, it's some simple imaging, and more often than not, that's including a CT scan these days, some measures to look for airway inflammation, and that may include things like FeNo measurement, but also spirometry and a review of the blood counts to look at eosinophil counts, and previous and historic eosinophil counts, to see where there's a type of pattern which might indicate someone who is responsive to inhaled or other types of steroid. And then generally, other investigations are guided particularly by the history. So I do perform laryngoscopy, but I tend to reserve that for people who've got something that worries me in that region of the neck. So I'm not performing laryngoscopy routinely. I may have missed some things, Surinder, let’s see what he says about his practice?

Professor Surinder Birring

Yes, thanks, Jim. It's very similar to yours. I would say that workup is fairly simple and basic for chronic cough. There's no need to use invasive or complex tests for most patients. I would like to flag the recent British Thoracic Society cough statement, or guideline, which was just published a couple of months ago, and it does signal a significant change from our past approaches to managing cough, to the key change being considering other conditions which we traditionally thought as causing cough, the reflux and asthma, as treatable traits, rather than causes. So these are comorbid or treatable trait conditions that can alleviate some of the cough, but they're not necessarily the cause. And the consequence of that is that our focus is shifting to a more direct approach at investigating rather than an empiric and systematic approach to investigating and treating everything that could possibly cause chronic cough. So these are the key changes in the British Thoracic guideline.

Professor James Hull

Surinder, perhaps you want to comment also about genetic tests, because you've done some amazing work recently, highlighting a new association, which I think many listeners may not be aware of. Yet, but it's, it's really fascinating.

Professor Surinder Birring

Yes it is fascinating. Jim and I have been working together on investigating patients with a rare neurodegenerative condition called CANVAS. It's a disorder of ataxia and peripheral neuropathy and vestibular problems. And in 2019 the gene for this condition was discovered, the RFC1. And what was fascinating was that one of the most common presentations of this condition is chronic cough, and it occurs 20 or 30 years before the other neurological symptoms such as numbness, neuropathic pain, and tingling. And so it really got Jim and I thinking about this condition, that there may be others in our chronic cough clinic, and we have just recently analysed our data, and in our clinic, about 8% of chronic cough have this gene that's potentially causing their chronic cough. But it also underpins our thinking of cough as a neuropathic disorder, and we also looked at the neurological symptom profile of patients in the cough clinic, and those with this RFC1 gene, and those without the gene, and unfortunately, the prevalence of neuropathic symptoms such as numbness and pain and tingling, it's very common in the cough clinic, so it's not easy to identify those who may have this genetic disorder.

So in our view, we have to test it, and the funding for this test has only recently been approved for a neuropathy and ataxia, but we've got more work to do to persuade NHS England to fund it for cough, because the discovery of this disorder and this genetic basis will hopefully improve our understanding of chronic cough and potentially lead to new treatments in future.

Host: Natalie Watson

Yeah, absolutely. Now you've just alluded to some treatments. So lots of treatment algorithms. We've discussed potential treatments for persistent throat symptoms from reflux, PPIs we've always traditionally been given. But of course, with the TOPPITS trial and they're now looking at the TALGiTS trial, whether or not PPIs are actually of any benefit if you've just got throat symptoms, the answer was no, no more benefit over placebo.

With regards to sinus problems, of course, nasal sprays, steroid sprays, and sprays, they can all be trialled. But what's your kind of treatment algorithm? Because there may be some GPS who'll be listening to this, and they'll obviously want to try things before sending into a tertiary referral centre.

Professor Surinder Birring

Yes, so treatment should first be addressing any treatable traits that are obvious, and avoid blind treatments of going looking for reflux rhinitis when there's nothing indicating that from the patient's history or assessment for asthma. The FeNo test is important, to measure airway inflammation, and it's becoming increasingly available in primary care, and it's usually available in most respiratory outpatient settings, and that avoids the need to try inhaled corticosteroids. But if it's not available, then a four week trial of an inhaled corticosteroid is reasonable, and the important thing is to review the patient and stop it. We see so many patients on these inhalers for years, when there's no reason to continue and they actually exacerbate the cough.

Host: Natalie Watson

Indeed, we see that a lot!

Professor Surinder Birring

Yeah, and for reflux, I think our British Thoracic Society guideline has shifted towards treating only those who have heart symptoms, so those without heart, there's no need to pursue a trial of a PPI, and that should reduce a lot of PPI use. And I think it's a very similar practice to persistent throat symptoms. It's a more directed approach, rather than treating everybody, because numerous PPI trials in chronic cough have been negative. And for rhinitis, James O'Hara T commissioner on the BTS panel, was very helpful, and we have recommended that treating chronic rhinosinusitis when present, but recognising that most patients with chronic cough have a persistent throat symptoms causing their upper airway profile, and not this elusive post nasal drip, it’s a symptom of hypersensitivity, rather than a sputum and mechanical problems.

Host: Natalie Watson

And it's this vicious cycle, isn't it? The throat clearing and changing, having a physical change, then on the larynx itself, and therefore perpetuating this inflammation cycle, and then hypersensing, increasing the sensitivity.

Professor Surinder Birring

If I could just bring in Jim, because he's an international expert on this EILO condition, and Jim, it occurs commonly in cough patients. But Jim, how do we recognise and treat that?

Professor James Hull

Well, thanks Surinder, that’s very kind of you. I mean, look, there's an awful lot of overlap. And actually, the work from Peter Gibson's group in Australia has shown that if you ask patients who have got, or seemingly present with just a chronic cough, about other throat related symptoms, and I'm sure lots of listeners here will know this better than me, and you ask them about whether the throat is closing, or whether they feel episodes around certain environments where they feel their throat closing, they can hear wheezy type sounds, it's actually very common, and there's overlap with voice disturbance and swallowing issues.

I think what that tells us is that probably these nerve fibre derangements, and these hypersensitivity processes, there's a lot of overlap in the pathways that lead to a mechanical output, it’s just slightly different in different people, and that's why often we use the terms laryngeal dysfunction ,and laryngeal sensitivity, as opposed to inducible laryngeal obstruction, which kind of implies there's just only one form of patterned behaviour.

Host: Natalie Watson

So focusing on that, thinking about, there's a treatment algorithm with regards to conservative, speech language therapy, and then obviously medications, as well as the surgical. Focusing on the lifestyle, conservative, speech language therapy and then medications. What's your treatment algorithm? Firstly, Jim?

Professor James Hull

Usually, by the time patients come to see me, they've had various different treatment trials that Surinder has talked about already, and I tend to use a combination approach, which uses speech and language therapy, because the study that Surinder and I did many years ago, showed that was a really effective treatment. And in fact, it has efficacy that is at least equal to some of the medicines that we have available to us at the current time, for example, drugs such as Gabapentin. So it's important, and it may also augment some of the drugs we use.

And then, of course, alongside that, the use of medications which target neural hypersensitivity. So I tend to explain that to patients in the way that I discuss migraine in that, you actually need a medication which might modulate neural activity and sensitivity, as opposed to us thinking about treating the reflux for other things that you've had before. It's a bit of a mind change in terms of, or a shift, in terms of the way that we approach this. And that starts the discussion about the different options of medicines that are available. And those listeners will know the options are not fantastic, and if I'm candid with people, working about a third of the time. So at the top of the tree, opiates probably are the most effective drug, but most associated with patient concern and side effects. And then lower down, a drug such as amitriptyline, gabapentin, pregabalin, neuromodulator drugs, all of which have some degree of associated side effect. But we are moving into exciting times in the world of cough, and new drugs are arriving, and Surinder has driven much of the research in this area. So I will hand back to him to say, what does the future hold for us? It's much more exciting?

Professor Surinder Birring

Thanks, Jim, the future is exciting! We, and others in the field, have been working towards a better understanding of the mechanisms of cough, this neuro hypersensitivity, and that's what's leading developments with new treatments. And the most exciting has been drugs that block the peripheral sensory nerves, the sensors in the cough reflex, and a particular receptor called the P2X3 channel. And this is a receptor that's normally activated by ATP, which is a neurotransmitter, and this is often released due to airway stress or injury, and this receptor can be blocked with medications. And, one called Gefapixant, has recently been licensed in Europe and Switzerland and Japan. And it’s  being used in Japan, and it's a waiting review for licensing in the UK. And then, if it meets that hurdle, it will then be reviewed by NICE for funding. So it has some way to go before it reaches patients, but that's an exciting treatment. It's a tablet. It's got a very good safety profile. It does have some side effects of taste disturbance, which are reversible if the patient had to discontinue. And there are other P2X3 drugs in clinical trial at the moment that are more selective for the cough receptor as opposed to the ACE receptor, so they have less taste side effects. And there's numerous other drugs, because there's so many different receptors and different types of nerves in the periphery, but in the airways, but also there are other drug targets in the brain that control cough mechanisms. So there's various receptors that present opportunities to develop drugs that target them, and there's multiple medications currently in the clinical trials.

So this is a shift towards recognising cough as a neural disorder, and developing treatments that target the defect and get it, and trying to get away from the drugs we have borrowed from other fields that Jim mentioned, like the morphines and the gabapentins, and are effective for some, but not for many, and do have lots of troublesome side effects.

Host: Natalie Watson

Brilliant. It sounds as though the future is bright for cough, and we're finding out a little bit more about it because of the wonderful work that you both do, and other specialists in cough around the world are doing. Are there any final thoughts or take home messages you would like to share with the listeners today?

Professor James Hull

Yeah, listen for people who are struggling with cough, we are still in a place where people often just assume that people want an answer in terms of, there's nothing on your chest X ray, but people don't appreciate how much this impacts patients. And so we must work harder to try and push their voice, and help them get access to the best treatments as soon as possible. And also to try and break this cycle where people get stuck, often, for many years, in a cycle of being treated for reflux, asthma, and nasal disease. And so as a community, we have to be able to accelerate people to the best drugs, and the new drugs particularly, far sooner, so they don't have to live with these miserable symptoms.

Host: Natalie Watson

And Surinder?

Professor Surinder Birring

The future is bright, and we're very excited, and we're getting close to new treatments becoming available for patients, but we still have some uncertainties, and unknowns, and we do need help from our patients in engaging with research, and clinical trials. There's a European Cough Patient Registry called NEuroCOUGH that they could participate in. There are patient advocacy groups that are being formed. There's likely to be many research trials and programs that patients can participate in to raise the profile of this condition and get access to treatments.

Host: Natalie Watson

So what we'll do is, we will put all of those links to everything aforementioned into the show notes. So if anybody does want to learn a bit more about cough, or be part of some clinical trials or anything, we can put any handy links in the show notes.

Thank you both so much for joining us today. You've both got very busy schedules, so I really appreciate you taking the time out to give us more information, and the up to date information about chronic cough from the respiratory perspective.

We hope you've enjoyed listening to BLA Connections: A Clear Voice. I've been your host Natalie Watson. Please do tune in this series, for more laryngology topics. We would also love to hear from you. Please feel free to email with any topics you would like us to explore, any questions you have, along with any suggested experts you would like to hear from. Also, if you'd like to contribute to these podcasts, please email enquiries@britishlaryngological.org

Our full series can be found in the podcast provider of your choice, or you will find all stored on our BLA Connect App for easy access. Thank you to all our listeners and we hope you found our podcast informative. Please remember to subscribe, and do leave a review with your podcast provider of choice. We do like your likes, subscribes, and reviews.