Chronic cough from laryngeal sensory neuropathy (LSN)

Laryngeal sensory neuropathy (LSN) is a recently described condition felt to cause a chronic cough in patients when treatment for everything else (allergies, asthma, reflux, etc) has been evaluated and managed.

Treatment for this condition is with neuropathic medications including Neurontin, Elavil, Lyrica, nortriptyline, etc.

In the past few months, I have seen a few patients referred to me with chronic cough treated with these medications with minimal or no improvement. All these patients reportedly had a full workup with everything being normal and as such, was diagnosed with LSN. These patients were being solely treated with neuropathic medications and nothing else.

On review of their old records, it became apparent to me that these unfortunate patients actually suffered from multiple causes of cough that was not being treated. A common condition missed or not treated in these patients was non-acid reflux which can only be diagnosed on 24-hour multichannel impedance testing. Another more common scenario was the presence of mild acid reflux and allergies based on minimal reactivity on allergy testing and reflux that was present, but within normal range on 24 hour testing. Medications for allergies and reflux were tried, but didn’t help and so was stopped. (Of note, none of the patients (prior to cough) ever had symptoms of reflux or allergies.)

Wrong. Treatment for both should have continued and very aggressively. Why?

Patients need to keep in mind that it is not unusual that a patient may have several factors of cough as well, all of which need to be treated in order to resolve a persistent cough. Because laryngeal sensory neuropathy results in a hypersensitized larynx, problems with reflux and allergies which ordinarily would not cause a cough (or any other symptoms) in normal patients, will now cause a persistent cough. (This situation is even applicable in patients who have NEVER had any symptoms of allergies and reflux in the past.)

In other words, though allergy testing may reveal only mild allergies and 24-hour pH study may show reflux episodes within normal range, these “mild” problems now need to be treated aggressively along with the neuropathy. To reiterate — laryngeal sensory neuropathy is a hypersensitized larynx. In this hypersensitized state, even a little bit of reflux or allergies will trigger a cough which normally would not. Each and every one of these conditions need to be treated aggressively to cure a persistent chronic cough.

The lack of treatment for each and every known cause of cough (even if mild) is the most common reason why treatment of laryngeal sensory neuropathy fails with neuropathic medication.

To illustrate, here is one case I saw a few months back.

Middle-aged patient who has had a chronic cough for about 15 years. Had a full workup done and found to have mild allergies to only alternaria mold (class 1) and dust (class 2). He did not respond to allergy medications and so these meds were stopped. Reflux workup did show significant reflux and so underwent nissen fundoplication which did help the cough by about 30%. His doctor than diagnosed him with LSN and tried him on a variety of neuropathic medication with some, but incomplete improvement. I was than asked to help figure things out.

The first thing I did was to instruct the patient to continue with the neuropathic medication that seemed to work the best for him (elavil 50mg twice a day). I also started the patient on allergy shots as well as an antihistamine and steroid nasal spray. I repeated a 24 hour pH and impedance testing to see if there was still reflux going on in spite of the reflux surgery. Lo and behold, there was both acid and non-acid reflux occurring, but on the high end of normal (much better than before his surgery). Based on this result, I restarted him on reflux medications daily.

Within 3 months, his cough completely resolved. I slowly tapered the elavil off. Once we both were convinced that his LSN was cured, the daily reflux medication was stopped and used only as needed. Allergy shots could have been stopped as well, but patient elected to continue them, but he no longer needed the daily allergy medications.

So, what happened?

This patient apparently had allergies, reflux, and laryngeal sensory neuropathy causing his cough. Given he was being treated for only LSN prior to seeing me, that was why he had incomplete improvement of his cough.

I aggressively treated for all 3 factors of his cough. The mild allergies and reflux were brought under tight control preventing them from constantly (even if mildly) irritating his hypersensitized voicebox. Once his voicebox was in an “clean” environment, it was able to heal and desensitize with Elavil. Once the voicebox was returned to a normal state, the reflux and allergy was now able to be treated like any other normal person.

The key thing to remember is that patients with LSN belong to a totally different sub-population of patients with a cough. One cannot treat them as if they are part of the normal population. “Normal ranges” of reflux and allergies do not apply which actually makes sense if one realizes the voicebox in patients with LSN is hypersensitized.

What if everything truly did come back normal?

There are 2 things I’ve done in this situation even when there’s absolutely no evidence for any abnormalities on any testing, mild or otherwise.

Botox injections to the thyroarytenoid muscle of the voicebox (similarly for spasmodic dysphonia treatment), starting combination therapy using two different neuropathic medications, each of which seemed to help singly.

Christopher Chang is an otolaryngologist who blogs at Fauquier ENT Consultants blog.

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  • Martin Young

    Thanks, Christopher – I find your post very helpful.

    I know of few other areas in our field that are as exasperating to treat, for both doctors and patients.

    I guess the message is to come out against chronic cough with all guns blazing, and for long enough!

  • Steven Park. MD

    A good review of treating intractable cough, and medically sound. I do agree that in most cases, chronic cough is from reflux that’s suboptimally treated. Reflux can be also aggravated by allergies, sinusitis, and other stomach problems.

    This approach will work in most cases, but there are a few important points that must be considered:

    Reflux medications do nothing to prevent your stomach juices from coming up into your throat. This is why why when you pound patients with BID PPI therapy for weeks to months, only some patients respond. When it works, it works really well. Some people have partial responses, and others have no response at all.

    What you have to realize is that what comes up into your throat (and nose and lungs) is not only acid, but also sometimes bile, digestive enzymes, and bacteria. All these other agents are very irritating to the throat. Less acidic juices in the throat can help some people, but not all.

    There are other true “reflux” medications but they’re not widely used due to the dominance of the PPI medication industry.

    In my experience, most people with chronic cough or laryngeal reflux have significant sleep-breathing problems. A significant number have true obstructive sleep apnea, but most just stop breathing at night occasionally, which is normal for most humans. You’ll also find that most people with these issues can’t or prefer not to sleep on their backs, since that’s when the tongue falls back due to gravity and when in deep sleep (due to muscle relaxation), it falls back and obstructs your breathing. This causes a vacuum effect that can literally suction up your normal stomach juices into your throat. This is why eating close to bedtime makes things much worse. The same with alcohol, since it relaxes your muscles.

    If you have any degree of nasal congestion (from allergies, colds, infections, deviated septum, flimsy nostrils) than that can aggravate tongue collapse even further.

    Repeated obstructions and arousals causes a low grade physiologic state of stress that causes your nervous system to become overly sensitive. This is why people with laryngopharyngeal reflux disease also have chronic rhinitis, where your nose is overly sensitive to weather changes, chemicals, scents or odors.

    When patients are given a Z-Pak for chronic cough or throat pain, some patients improve dramatically, but only temporarily. The macrolides have an anti-inflammatory effect by helping to empty the stomach faster. I remember in general surgery we gave IV erythromycin to stimulate bowel movement. This is also why long-term clarithromycin has been found in some studies to significantly improve chronic sinusitis. One study showed that sudafed and domperidone (a pro-motility agent) significantly helps snoring and symptoms of obstructive sleep apnea.

    Since by definition, all modern humans have some degree of dental crowding and upper airway narrowing, all these issues with reflux, lack of efficient sleep, nasal/sinus problems are not surprising. Inflammation in the nose and throat causes further narrowing, aggravating things even further. If you still have tonsils, it’ll swell up causing more obstructions, suctioning up more juices.

    The first step is to optimize nasal breathing by whatever means, and lessen inflammation in the throat by avoiding eating or drinking alcohol close to bedtime. Many people will respond with conservative options, but for the people that don’t, if you address the underlying sleep-breathing issues in a step-wise manner, not only can the cough get getter, but their sleep quality and their overall state of health can improve dramatically.

    Although Dr. Chang’s approach does work and is advocated by many of the experts in our field, it still only treats the symptoms and not the cause. I’m willing to bet that years later the symptoms will recur and you’ll have signs of obstructive sleep apnea. Many of these patients will already snore, and almost routinely, one or both parents snore heavily.

    The hypersensitive reflex that causes cough in the initial stages is likely to transform later into a hyposensitive state, where the chemo and baroreceptors in the throat become hypoactive due to chronic reflux exposure, which can later promote longer breathing pauses, eventually progressing up the sleep-breathing continuum into obstructive sleep apnea.

    Although neuropathic medications for these conditions are becoming “standard of care”, this is similar to giving a pill for anxiety, which doesn’t really treat the cause—it only covers it up.

  • Dan

    Thanks. As a chronic morning-cougher, your diagnosis is what I’ve been saying for years about the causes of my cough. The 5- or 10-minutes of coughing, 30 or so minutes after I wake up, has been part of my morning routine for many years. Question: Since I am so used to it, what’s the downside to leaving the cough untreated (other than the otc med I take foe the reflux)?

  • Martin Young

    Remember pepsin can also cause reflux laryngitis and is not influenced by PPI’s. I always prescribe sucralfate to bind the pepsin and help minimize non-acid reflux. Another important point is that PPI’s work by preventing the stomach making acid in response to food – i.e. unless taken well before meals they will not work!!

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