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
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.
THE PATHOPHYSIOLOGY OF LPR IS POORLY UNDERSTOOD
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.
CURRENT DIAGNOSTIC TESTS FOR LPR HAVE SHORTCOMINGS
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.