Laryngopharyngeal reflux: More questions than answers

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ABSTRACTLaryngopharyngeal reflux (LPR), an extraesophageal variant of gastroesophageal reflux disease, is associated with hoarseness, chronic cough, throat-clearing, sore throat, and dysphagia. But because these symptoms are nonspecific, laryngoscopy is often done and the diagnosis of LPR is considered if edema, erythema, ventricular obliteration, pseudosulcus, or postcricoid hyperplasia is noted. Most patients with suspected LPR are given a 2-month trial of a proton pump inhibitor. Yet there is still little or no solid evidence on which to base the diagnosis or the treatment of LPR. We review the current understanding of the pathophysiology and discuss current diagnostic tests and treatment regimens in patients with suspected LPR.


  • Laryngoscopy has high interrater variability, and results of pH monitoring do not reliably predict who will respond to treatment.
  • A proton pump inhibitor twice daily for 2 months is currently recommended for patients with laryngeal signs and symptoms. If the condition responds to therapy, tapering to once-daily therapy and then to minimal acid-suppression to control symptoms is prudent.
  • Patients whose symptoms do not respond to a proton pump inhibitor are unlikely to benefit from surgery. Other diagnoses should be entertained, while the drug is tapered to prevent rebound acid reflux.



The scenario is common: a patient complains of chronic hoarseness, cough, throat-clearing, sore throat, dysphagia, or a lump in the throat and undergoes laryngoscopy. If this test rules out cancer, the patient is given a diagnosis of laryngopharyngeal reflux (LPR), ie, a form of gastroesophageal reflux disease (GERD) in which the stomach contents get all the way up into the pharynx and down into the larynx. A proton pump inhibitor (PPI) is often prescribed, usually twice daily for 2 months.1–6

Unfortunately, the diagnosis and treatment of LPR remain controversial in the absence of solid evidence from randomized, placebo-controlled trials. The signs and symptoms (Table 1) are not specific, and even though the diagnosis of LPR is considered if edema, erythema, ventricular obliteration, pseudosulcus, or postcricoid hyperplasia is documented on laryngoscopy,4 interpretation of the laryngoscopic features is subjective.

In this article, we review the current understanding of the pathophysiology of LPR and evaluate current diagnostic tests and treatment regimens for patients with suspected LPR.


Transient relaxation of the lower esophageal sphincter

In a study in 10 healthy volunteers, Dent et al7 found that the pressure in the lower esophageal sphincter varies considerably over a 12-hour period. Episodes of reflux were not related to low basal (resting) pressure. Rather, 70% to 100% of reflux episodes occurred during random episodes of transient, complete, and inappropriate relaxation of the sphincter that lasted about 5 to 30 seconds. The mechanism of this relaxation is not known but is thought to be related to activation of the vagus nerve, possibly as a consequence of gastric distention.8

Gastric, not duodenal products seem to cause the damage

In a study in dogs, Adhami et al9 evaluated the possible role of gastric juices (acid and pepsin) vs duodenal juices (bile acids and trypsin) in laryngeal tissue damage. After taking baseline biopsy samples of the larynx, the investigators applied a variety of gastric and duodenal enzymes at varying pH levels (pH 1–7) to the larynxes. After 9 to 12 applications, they took another biopsy and assessed the changes visually and histologically.

At low (ie, acidic) pH levels, pepsin and conjugated bile acids were the most injurious, causing erythema and histologic evidence of inflammation. The authors concluded that gastric and not duodenal substances cause laryngeal injury and that acid-suppressive therapy “should eliminate the injurious potential” of acid reflux.9

The larynx is more sensitive than the esophagus

Monitoring of esophageal pH has shown that healthy people can tolerate as many as 50 episodes a day of acid reflux (pH < 4) in the esophagus. However, Koufman10 found that as few as three episodes of laryngeal reflux per week can cause severe laryngeal inflammation and injury.

Does pepsin deplete buffers, worsening acid damage?

Johnston et al11 took biopsies from a control group of healthy volunteers and from patients diagnosed with LPR. They detected pepsin in the samples from eight of the nine patients with LPR but in none of the controls. Furthermore, the tissue from patients with LPR had low levels of carbonic anhydrase III. The authors hypothesized that pepsin depletes the laryngopharynx of carbonic anhydrase III, and that therefore these tissues cannot produce enough bicarbonate to buffer the gastric acid. Less bicarbonate would mean greater acidity, so the pepsin would remain active and would be more likely to cause cellular damage.11

However, this contention is controversial. What is universally agreed upon is that reflux of gastric or gastroduodenal contents is most likely causing injury, most likely through direct exposure, although indirect effects through vagal mechanisms cannot be ruled out.


The diagnosis of LPR has become more common over the last few years,4 and by some estimates up to 10% of patients presenting to ear-nose-throat physicians have complaints related to GERD.12 However, current diagnostic tests for reflux and LPR have many shortcomings and can lead to misdiagnosis of this disease (Table 2).

A careful history is important. Many patients report they have sore throat, hoarseness, cough, dysphasia, or chronic throat-clearing.13 Factors that may predispose a patient to esophageal reflux should be discussed, eg:

  • Tobacco use
  • Diet (eg, soda, spicy foods, fatty foods)
  • Alcohol use
  • Certain drugs (calcium channel blockers, nitrates, steroids).

Up to 50% of patients presenting with extraesophageal symptoms may not have classic reflux symptoms such as heartburn and regur-gitation.14 However, the existence of “silent reflux” is currently controversial.

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