Things to Remember
When Chronic Cough Becomes the Problem Itself
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Chronic cough can become self-perpetuating: After the original trigger (viral infection, asthma, reflux) is treated, the cough itself can continue by re-irritating airways and creating a nervous system loop where "the brain learns to cough."
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Refractory chronic cough affects 20-40% of chronic cough patients: These cases persist despite appropriate treatment of underlying causes, with the cough reflex itself becoming hypersensitive rather than being a symptom of another disease.
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Cough hypersensitivity syndrome involves nerve sensitization: The vagus nerve becomes hyperexcitable, lowering the cough threshold so normal triggers (talking, laughing, temperature changes, perfume) provoke coughing - the protective reflex becomes a hair-trigger response.
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The cough creates a self-sustaining cycle: Repeated forceful coughing causes microtrauma to airways, sustaining inflammation that keeps nerves sensitized, which triggers more coughing - along with a learned psychological/neurological component.
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Diagnosis requires ruling out serious causes first: Workup includes chest imaging, spirometry, and sometimes bronchoscopy, but about half of chronic cough cases have no identifiable underlying cause after full evaluation.
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Speech pathology/cough suppression therapy is first-line treatment: Trained therapists teach breathing techniques to recognize and suppress the cough urge, breaking the cycle - studies show ~40% reduction in cough frequency.
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Neuromodulator medications are second-line options: Gabapentin and pregabalin can dampen nerve excitability when behavioral therapy alone doesn't provide sufficient relief.
This article explains why some coughs persist long after the initial cause is gone, how the cough itself becomes the problem, and what can be done to break the cycle.
Sometimes the cough stops being about what caused it. That's the part that's hard to explain. Someone will come in - or call me - months into a cough that started reasonably enough. Post-viral, maybe asthma, possibly reflux. We treated the original trigger. The tests came back normal. The medications helped a bit. But the cough stayed.
At some point, the cough became self-sustaining. The airway stayed irritated not because of what started it, but because the coughing itself kept re-irritating the tissues. The nervous system got stuck in a loop. The brain learned to cough.
This is refractory chronic cough - cough that persists despite appropriate treatment of underlying causes. And it's more common than you'd think. Roughly 20-40% of people with chronic cough fall into this category. They've tried the reflux medications, the asthma inhalers, the allergy treatments. Everything that should work. And yet the cough remains.
What's going on there is fascinating. And frustrating. And only recently starting to make sense.
The Cough Hypersensitivity Syndrome
For a long time, we thought of chronic cough as a symptom - a flag pointing toward some underlying disease. Treat the disease, resolve the cough. Simple enough.
But somewhere in the last 15 years, researchers started noticing patterns in people whose cough wouldn't respond to standard treatments. Their airways were hypersensitive to triggers that wouldn't normally provoke coughing. Talking. Laughing. Temperature changes. Perfume. Even just taking a deep breath.
They called this cough hypersensitivity syndrome - the idea that chronic cough, in many cases, isn't just a symptom of something else. It's a disorder of the cough reflex itself. The sensory nerves in the airway become hyperexcitable. The threshold for coughing drops. What used to be a protective reflex becomes a hair-trigger response.
The physiology is complex, but it comes down to this: the vagus nerve - the main nerve that controls cough - gets sensitised. Inflammatory mediators, viral infections, acid reflux, even the mechanical trauma of coughing itself can upregulate receptors on these nerve endings. TRPV1 receptors, for instance - they respond to capsaicin, cold air, acid. When they're upregulated, everything starts to feel like a threat.
The airway becomes hypervigilant. And once that happens, treating the original cause doesn't always reset the system.
Why Some Coughs Get Stuck
I've seen this play out in different ways. Someone gets a respiratory infection - RSV, parainfluenza, something that lingers. The infection clears, but the cough doesn't. We check for asthma. We trial reflux medications. We scan the sinuses. Everything comes back unremarkable. Or slightly positive, but not enough to explain the severity.
What's happened is the cough itself has become the pathology. The repeated mechanical insult - hundreds of forceful exhalations per day - causes microtrauma to the airway lining. That trauma sustains low-grade inflammation. The inflammation keeps the nerves sensitised. The sensitised nerves keep triggering cough. It's a loop.
And there's a psychological component too, though saying that out loud sometimes makes people defensive. I don't mean it's "in their head" - I mean the brain learns patterns. Cough becomes conditioned. You walk into a cold room, or you smell something strong, and before you consciously register it, you're coughing. The brain has learned to expect it.
There's good evidence for this. Studies using cough challenge tests - where people inhale capsaicin or citric acid - show that individuals with chronic cough have a much lower cough threshold than healthy controls. Their C-fibers - the small nerve fibers that detect irritants - are more excitable. And interestingly, this hypersensitivity can persist even after the underlying trigger resolves.
One study in Thorax (2020) found that about half of people with chronic cough had no identifiable cause after full workup. The cough itself was the disease.
How We Approach Refractory Cough
When someone's been coughing for months despite appropriate treatment, we start thinking differently. First, we make sure we haven't missed anything serious. Chest X-ray, sometimes CT. Spirometry. Sometimes methacholine challenge - a test that provokes airway narrowing to detect hidden asthma. Occasionally bronchoscopy - a camera scope into the airways - if there's concern for structural abnormalities or foreign bodies.
But if all that's clear, we shift focus. We stop chasing zebras and start treating the cough reflex itself.
Speech Pathology and Cough Suppression Therapy
This sounds strange to people at first. Speech pathology for a cough? But it works. Cough suppression therapy - sometimes called cough retraining - teaches people to recognise the early sensation of needing to cough and suppress it using controlled breathing techniques.
The idea is to break the cough cycle. You feel the urge, but instead of coughing, you do a slow nasal breath and a swallow. Or a soft throat clear. Small, gentle actions that don't traumatise the airway. Over time, the nervous system recalibrates. The threshold shifts back.
Multiple RCTs - randomised controlled trials, the gold standard for evidence - have shown this works. One Australian study published in CHEST (2021) found that speech pathology reduced cough frequency by about 40% in people with refractory chronic cough. That's significant. Not a cure, but meaningful improvement.
I refer people to speech pathologists trained in this. It takes a few sessions. Sometimes weeks. But for people who've been coughing for six months straight, a 40% reduction feels like freedom.
Neuromodulators: Gabapentin and Pregabalin
If behavioural therapy alone doesn't work, we sometimes trial medications that dampen nerve excitability. Gabapentin and pregabalin - originally developed for neuropathic pain and epilepsy - work by calming overactive nerve signalling.
The mechanism is interesting. They bind to voltage-gated calcium channels on sensory neurons, reducing the release of excitatory neurotransmitters. In plain terms: they turn down the volume on hypersensitive nerves.
Studies show gabapentin can reduce cough severity by about 40-50% in refractory cases. A meta-analysis in The Lancet Respiratory Medicine (2022) pooled data from several trials and confirmed modest but real benefit. The side effects - dizziness, fatigue, sometimes cognitive fog - limit its use, but for people whose cough is ruining their life, it's often worth trying.
Pregabalin works similarly but has slightly different pharmacokinetics - it's absorbed faster, reaches peak levels quicker. Some people tolerate one better than the other. We usually start low and titrate slowly.
The Emerging Role of P2X3 Antagonists
This is where the science gets exciting. In the last few years, researchers identified a specific receptor - P2X3 - that seems to play a major role in chronic cough. It's expressed on sensory nerve endings in the airway and responds to ATP, a molecule released during tissue injury and inflammation.
When P2X3 receptors are activated, they trigger cough. And in people with chronic cough, these receptors are upregulated. Block the receptor, and you block the cough.
Gefapixant is the first P2X3 antagonist approved for refractory chronic cough. It was approved in Europe and Japan in 2022, and the FDA is currently reviewing it. The trials showed significant reductions in cough frequency - about 20-30% more than placebo. That might not sound like much, but for people who've tried everything else, it's substantial.
The main side effect is taste disturbance - about 70% of people on gefapixant report altered taste. Metallic, bitter, sometimes just dulled. For some, it's tolerable. For others, it's a dealbreaker.
But the fact that a targeted therapy like this works tells us something important: chronic cough, in many cases, is a neurophysiological disorder. It's not just inflammation. It's not just reflux. It's the nervous system itself.
When to Suspect Something Else
Before we commit to treating refractory cough, we have to be sure we're not missing something rarer. Red flags change the game:
- Haemoptysis - coughing up blood. Always needs imaging, often bronchoscopy. Could be infection, malignancy, vasculitis, bronchiectasis - abnormal widening of the airways that traps mucus and leads to recurrent infections.
- Weight loss - unexplained weight loss with chronic cough raises concern for TB, cancer, chronic infection.
- Night sweats - classic for TB, also seen in lymphoma.
- Progressive dyspnoea - worsening shortness of breath suggests interstitial lung disease, heart failure, or progressive airway disease.
- Smoking history - especially heavy or long-term. COPD, lung cancer, chronic bronchitis all more likely.
- Immunosuppression - HIV, chemotherapy, transplant patients. Opens the door to opportunistic infections like fungal disease or atypical mycobacteria.
If any of those are present, we don't treat empirically. We investigate.
The Psychological Toll
People don't talk enough about what chronic cough does to someone's life. I've had patients who stopped going to movies because they knew they'd start coughing and disturb everyone. Who avoided restaurants. Who felt self-conscious at work. One person told me they stopped going to their grandkid's school plays because the coughing made them feel like a disruption.
There's a validated quality of life questionnaire - the Leicester Cough Questionnaire - that measures the impact of cough on physical, psychological, and social functioning. Scores in people with chronic cough are often worse than in people with moderate COPD. That's not trivial.
And yet, when I ask people what bothers them most, it's not always the physical discomfort. It's the embarrassment. The feeling that they're annoying everyone around them. The constant apologising.
I've noticed that the psychological burden sometimes makes the cough worse. Anxiety can lower the cough threshold. Stress upregulates inflammatory pathways. The mind-body loop reinforces itself.
What We Know Now (And What We Don't)
The landscape of chronic cough has shifted. Ten years ago, if someone didn't respond to reflux medication or asthma inhalers, we'd just keep trying different combinations and hope something stuck. Now we understand that some coughs are self-perpetuating. The reflex itself becomes disordered.
That changes how we treat it. We target the nervous system. We retrain the reflex. We use medications that modulate nerve excitability, not just suppress inflammation.
But there's still a lot we don't know. Why do some people's coughs resolve after a viral infection and others don't? Why do some respond to gabapentin and others don't? What predisposes someone to developing cough hypersensitivity in the first place?
Genetics probably plays a role. So does prior airway injury. Possibly early-life respiratory infections. There's emerging research on the microbiome - the community of bacteria in the airways - and whether dysbiosis contributes to chronic inflammation and nerve sensitisation. It's early days, but interesting.
Practical Takeaways
If you've been coughing for more than eight weeks:
- Rule out the common causes first - asthma, reflux, medications, postnasal drip. Most chronic cough is one of these.
- If standard treatments don't work, consider cough hypersensitivity - especially if you're coughing in response to triggers like talking, cold air, or strong smells.
- Speech pathology isn't pseudoscience - cough suppression therapy is evidence-based and can significantly reduce cough frequency.
- Neuromodulators can help - gabapentin or pregabalin are options if behavioural therapy alone isn't enough.
- Red flags matter - blood, weight loss, night sweats, progressive shortness of breath. Don't ignore them.
Chronic cough is frustrating. For the person living with it, and sometimes for the doctor trying to figure it out. But we're getting better at understanding it. And better at treating it.
Not every cough resolves completely. But most improve. And for people who've been coughing for months, even a 40% reduction changes everything.
