Some clinicians, primarily gastroenterologists, doubt the existence of laryngopharyngeal reflux. But many otolaryngologists-head and neck surgeons and others have accepted the idea that, although it is related to and sometimes occurs in patients with gastroesophageal reflux disease, laryngopharyngeal reflux (LPR), the backflow of gastric contents into the laryngopharynx, stands alone as a disease.
Explore This IssueMay 2006
Distinguishing the Condition
A group of symptoms, principally excessive throat clearing, persistent cough, globus pharyngeus (sensation of lump in the throat), and hoarseness, usually suggests LPR. Other symptoms of LPR may include dysphagia, postnasal drip or excess throat mucus, breathing difficulty or choking spells, and sore throat. All may be chronic or intermittent. Unless the patient also has gastroesophageal reflux disease (GERD), which some 20% do, heartburn is not present.
Non-specific but often associated signs seen on laryngoscopy include an inflamed larynx, pseudosulcus, and contact granulomas. Esophagitis is not usually present unless, again, the patient also has GERD.
In 1991, Jamie A. Koufman, MD, currently Professor of Otolaryngology at Wake Forest University School of Medicine in Winston-Salem, NC, and soon to become the first director of the Voice Institute of New York, was the first to state that LPR is a disease on its own-that reflux of gastric contents can indeed occur in the larynx causing these specific symptoms. She demonstrated this by ambulatory pH monitoring showing that acid is often present in these patients’ throats, and by other studies.
The culprit is believed to be a dysfunctional upper esophageal sphincter (cricopharyngeus), which allows gastric contents to move from the esophagus into the throat and even up into the nose or sinuses or down into the trachea and lungs. Indeed, many asthma patients also have reflux as a significant co-factor, according to Dr. Koufman. We have sometimes seen a chemical-type burn along the lung lining and the trachea, she said.
The theoretical basis for this is very sound. The larynx is not well protected with carbonic anhydrase-releasing enzymes and so it’s going to be damaged if even a little squirt of stomach acid which includes pepsin gets up there. – -Charles N. Ford, MD
Bringing LPR Out of the Shadows
Nonetheless, it has taken some time for LPR to emerge not only from the shadow of GERD but as a disease susceptible to specific diagnostic criteria and treatment. One difficulty, according to Charles N. Ford, MD, Professor and Chair of the Division of Otolaryngology-Head & Neck Surgery at the University of Wisconsin Medical School in Madison, is that in recent years there has been an overcall of this disease. Lack of appreciation for the fact that smoking, alcohol abuse, toxic inhalants, allergies, postnasal discharge, vocal overuse, and even infections can mimic mild LPR and that laryngoscopic signs can occur in asymptomatic people has occasionally led to such over diagnosis. This in turn has led some gastroenterologists to question whether LPR is real.
Pepsin, activated by acid, is the damaging factor in both reflux conditions, Dr. Koufman told ENToday. The theoretical basis for this is very sound, added Dr. Ford, because the larynx is not well protected with carbonic anhydrase-releasing enzymes and so it’s going to be damaged if even a little squirt of stomach acid which includes pepsin gets up there. But there are no anti-peptic drugs, so H2 antagonists or, more commonly now, proton pump inhibitors are the treatments of choice for both conditions. In fact, with LPR, a good response to PPIs can confirm a diagnosis suggested by the symptoms.
Tools for Diagnosis
One diagnostic aid is the Reflux Symptom Index (see left). Designed by Dr. Koufman, Peter Belafsky, MD, and others, it can be administered to patients both before and after initial treatment to confirm the diagnosis. Patients grade a list of possible LPR symptoms on a 0 to 5 point scale; a score greater than 13 strongly suggests the presence of LPR.
The importance of various laryngoscopic findings in the LPR diagnosis can be assessed with the Reflux Finding Score, also designed by the Wake Forest group (see right). This scale rates eight possible LPR-associated signs on a variably weighted score of 0 to 4: subglottic edema, ventricular obliteration, erythema/hyperemia, vocal fold edema, diffuse laryngeal edema, posterior commissure hypertrophy, granuloma, and thick endolaryngeal edema. A score of 7 or higher yields a 95% certainty that LPR is present.
The definitive approach to confirming LPR is pH monitoring, specifically ambulatory 24-hour double-probe (simultaneous esophageal and pharyngeal) pH monitoring. The simplest of such devices have sensors just above the lower esophageal sphincter and just where the esophagus opens into the hypopharynx. The placement of these tubes is very important, noted Dr. Ford, because if the top is too high it gets exposed to air, which gives a false reading, or to enzymes in the mouth that neutralize the acid.
Also available are tubes that have sensors all along this distance. The more sophisticated version, which is the multichannel impedance test, measures not only liquids that come up from stomach but also gases, and it’s possible with this device to monitor and recreate on a computer the whole process of materials going up and down the esophagus, Dr. Ford said. The sensors let you know the resistance between the walls of the esophagus. If the patient is not swallowing there’s very little resistance. If he patient does swallow, a bolus of air goes through, separating the walls and giving maximum resistance. Fluids give another reading entirely. So if gases ascend and foods ascend they can be differentiated and, in addition, the pH can be measured at those levels.
Room for Improvement in Diagnostic Methods
Dr. Ford added, though, that this sophisticated and sensitive multichannel impedance device has only been around for a few years, so experience is somewhat lacking. Practice is essential. Also, the software programs aren’t well worked out yet, so use of the device is labor intensive. Most often, gastroenterologists rather than otolaryngologists place the device. If it’s positive or the pH test is positive, the patient probably has reflux.
There is debate about what constitutes a positive study; some work suggests that it takes less acid or a shorter length of exposure to acid high in the larynx to cause irritation than in the esophagus. Thus, although a drop in pH to 4 has been used for years to indicate the presence of GERD, there is pretty good evidence now to suggest that acid exposures to down to 5 are significant in the larynx, stated Dr. Ford.
Actually, according to Dr. Koufman, the best test is an experienced clinician. Patients with abnormal symptoms or findings or pH tests or biopsies are easy. But sometimes patients whom we think have the disease have a normal pH study, which just means that they had a good day. Sometimes the pH device actually helps the reflux because some people find it so irritating that they swallow continuously and the more you swallow the more you drive the system and cut down on reflux.
Waiting in the wings, however, is a pepsin immunoassay for diagnosis of LPR. Commercialization of the assay may come relatively soon, according to Dr. Koufman, who holds the patent. There is a need to have something highly objective and indisputable where you can say, with a simple test, ‘Yes, the patient has LPR’ or not, Dr. Ford explained.
It will be another generation before we have a complete understanding of LPR. – -Jamie A. Koufman, MD
Treatment Options Similar to GERD’s
Although patients with mild or intermittent LPR symptoms may improve after making dietary or lifestyle modifications or taking an H2 antagonist, the majority of LPR patients seem to do best with twice daily dosing of PPIs The reason: none of the PPIs exert acid suppression (intragastric pH >4) for more than 16.8 hours. Some patients do even better when an H2 antagonist is added. In many, the minimum initial treatment period with PPIs is six months. Some may have to take these drugs for extended periods.
‘Not All That’s Red’ is LPR
For gastroenterologist Michael F. Vaezi, MD, PhD, Professor of Medicine and Clinical Director of the Division of Gastroenterology and Hepatology at Vanderbilt University School of Medicine in Nashville, TN, a problem arises when suspected LPR patients don’t respond to PPIs. I believe there is such a thing as reflux laryngitis or LPR, Dr. Vaezi told ENToday. I believe that patients who respond to PPIs have the disease and we should treat them as such. But the controversy centers around the nonresponders. [Some] consider everything that’s red in the throat as reflux. But not all that’s red is GERD.
Most otolaryngologists would agree that a red larynx, which can be caused by many factors, is not pathognomonic of LPR.
There’s a real difference in the patient populations seen by otolaryngologists and gastroenterologists, Dr. Ford pointed out. Gastroenterologists don’t see the patients who complain of postnasal drip, hoarseness, throat clearing, and so forth. The ones they do see are the ones that frustrated otolaryngologists send to them saying that the patient was treated with PPIs and didn’t get better so try to take care of them. In fact, the patients who don’t respond to PPIs often have other things going on.
For example, such a patient may have a really bad hiatal hernia and the dynamics of the esophagus are off and waves are going up and down and he could be getting reflux material into his larynx which is not acid. There was a nice paper last year by C.T. Sasaki and colleagues who studied refluxate in an animal model and found that alkaline material such as bile salts could irritate the larynx. In such instances, surgery such as fundoplication might be helpful.
Indeed, fundoplication is an option for patients believed to have LPR who don’t respond to PPIs or are unable to take them. Said Dr. Koufman: Some patients, for example, may wake up in the middle of the night coughing and gasping for air. For them, surgery can be life-changing.
Treatment Key for Preventing Complecations
Finally, in a recent paper in JAMA (2005; 294: 1534-1540), Dr. Ford warns of the possible danger of neglecting LPR: When a medical practitioner fails to recognize LPR, patients have prolonged symptoms and delayed healing. Inflamed laryngeal tissues are more easily damaged from intubation, have a greater risk of progressing to formation of contact ulcers and granulomas, and often evolve to symptomatic subglottic stenosis and lower airway disease. In a recent report, LPR symptoms were found to be more prevalent in patients with esophageal adenocarcinoma than were typical gastroesophageal reflux symptoms and they often represented the only sign of disease.
Laryngeal cancer is another specter hovering over LPR. Dr. Koufman said that she has reported a series of 50 patients with laryngeal cancer, 76% of whom had reflux disease. Only 22 were active smokers; 21 were past smokers with a median smoking duration of eight years, and seven were non-smokers. A few other studies have had similar findings.
Despite the progress, Dr. Koufman believes that it will be another generation before we have a complete understanding of LPR.
©2006 The Triological Society