COMMENTARY

Neurogenic Cough: New Insights

David A. Johnson, MD

Disclosures

September 12, 2018

A Cough's Hidden Cause

Hello. I'm Dr David Johnson, professor of medicine and chief of gastroenterology at Eastern Virginia Medical School in Norfolk, Virginia. Welcome back to another GI Common Concerns .

In a recent video, I highlighted the excellent work of Vaezi and colleagues in detailing the extraesophageal complications of gastroesophageal reflux disease (GERD) and where the pendulum may be swinging. I provided a couple pearls from my own experience, the last of which relates to coughing and how gastroenterologists can evaluate it.

This topic is substantial enough that I felt compelled to return to it, because it is something that we see not infrequently as gastroenterologists. I want to amplify some of those prior messages and also give you some new tips from my own clinical experience.

Ruling Out and Considering Something New

Cough represents a possible reflux referral, with patients sent to us from multiple [clinicians] (primary care, allergists, or pulmonologists). The most common causes of cough presenting with a clear chest x-ray and no underlying pulmonary disease are GERD, postnasal drip, and asthma.

When a patient presents with cough from unknown origins, gastroenterologists are often tasked with evaluating them with pH monitoring or an empiric trial of a proton pump inhibitor (PPI), which we know has little value. This was proven in a well-designed randomized controlled trial by Shaheen and colleagues,[1] who showed this even using [twice-daily] dosing. GERD, in the absence of symptoms of reflux and heartburn, is not predictive for cough. Nonetheless, those are pathways by which patients come to us.

So, what are we dealing with in these patients?

To begin, you should get familiar with the term "neurogenic cough." What I mean by this is that these patients may have an inciting event. It doesn't matter if it's reflux, postnasal drip, or maybe a postviral syndrome. What matters is that they now have persistent cough, which the [American College of Chest Physicians] defines as unexplained cough in excess of [8 weeks][2] and the other parameters we've discussed (eg, clear chest x-ray).

Neurogenic cough means that the patients have become acclimatized to a cyclic cough. They have repetitive and persistent paradoxical vocal cord movements, which may result from prolonged talking, vocal cord stress, voice inflection changes, or whatever they're perceiving as sensory abnormalities that lead to this ongoing trigger for and hypersensitization to cough. Patients may precipitate this by trying to clear their throat and then coughing. As a result of simply coughing, inflammatory mediators are upregulated by the physical mechanics. This puts the patient into a cycle of repetition.

Identifying a Neurogenic Cough

We may commonly see patients who present with this type of cough. I've had three such cases just in the past month.

First, I take a good history to ensure I'm not missing something as it relates to an underlying pulmonary or ear-nose-and-throat condition. If those are present, we treat them as best we can, but once that is done you're left with this patient with cough.

We can't just send them back with a pH monitor. These may be very misleading, as patients don't routinely correlate their cough with a reflux episode. There are ways to enhance their accuracy, such as with acoustic pH monitors that have been evaluated specifically for this type of indication.

We don't always have a good symptom index when we talk about cough. In the absence of heartburn or ongoing reflux, it's really hard to say that they certainly need ongoing therapy for this. However, we're then left with the option of telling these patients that it's not reflux, so we're sending them back to their primary care doctors for an ongoing cough that just doesn't go away. I think we can do better than that. If you, as a gastroenterologist, understand the concept of neurogenic cough, you can perhaps do something good for these patients.

After taking a good history, I look for habituation. Patients clearly need to have an evaluation for repetitive throat clearing. I bring the relevant family member(s) in and discuss identifying precipitating events that cause the cough. Perhaps it's laughing or they're coughing more at night because they've been talking on the phone all day. Then I'll look for other things that may trigger them, such as environmental factors like temperature changes.

After that, you're left with a neurogenic cough. The next step is to attempt to downregulate the sensitization.[3,4] Once I control these other contributors, I'll often have a patient see one of our voice rehabilitation specialists or speech pathologists. They can look at ways to control the urge to cough, such as a deep breathing exercise or a swallow response evaluation for paradoxical vocal cord movements, while you work on the neurogenic component.

Treatment Strategies

The evidence on what to do next is pretty sparse.

According to 2016 guidelines[2] from the [American College of Chest Physicians], the neurogenic component of cough may be treated with a variety of medications; gabapentin (Neurontin) or pregabalin (Lyrica) have been looked at. But again, the data are sparse, and certainly there are no randomized controlled trials to guide us.

I've found some of the tricyclic antidepressants like amitriptyline to be helpful. I prescribe a low dose to be taken at bedtime for the potential somnolence effects. I'll start with 25 mg of amitriptyline, which I'll maintain for 2-3 months as I monitor for its benefit.

Recently I've been using tramadol, based on the recommendation of a colleague, a voice-trained laryngologist. It's a great approach, though data on this are extremely limited. There is one pilot study[5] that used a very high dose of tramadol (50 mg, three times a day), which is what my laryngologist uses. In my patients, I've found it not quite necessary to be as aggressive in the dosing. Instead, I use a different dose that I find has been extremely helpful. I'll start with 25 mg at bedtime, again for the somnolence benefits of this narcotic analog. After 3-5 days, if they're not showing some improvement, I'll ask them to increase it to twice a day.

Once I can get them to the point where the cycle of coughing is broken, then I want to wean them down. We must recognize that tramadol is an addictive medication, so I try and get them off very quickly. If I started them at bedtime, I'll halve the dose and stop it after about 1-2 months.

The tramadol trick is one that I've found to be enormously successful and helpful, and why I wanted to share it with you as well. I recommend you consider it after assessing the potential risks and benefits.

Once you break the coughing cycle, you'll find that these patients can learn other elements of the neurogenic cough-directed treatment very successfully. They can obviate repetitive throat clearing and undergo voice rehabilitation, among other things, to aid this process.

I'm not suggesting by any means that we serve as laryngologists or supplant the role of our pulmonologists or otolaryngologists. Just recognize that you may be the final common pathway to the patient who still has no answer to why they're coughing. It is time for us to step up in these situations.

I'm Dr David Johnson. I look forward to chatting with you again soon. Thanks again for listening.

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