The potential use of pepsin and carbonic anhydrase isoenzyme III (CA-III) as diagnostic markers for laryngopharyngeal reflux disease.

An increasing weight of clinical evidence suggests that reflux of gastric contents into the laryngopharynx (laryngopharyngeal reflux [LPR]) contributes to the pathophysiological characteristics of a number of nonspecific otolaryngological inflammatory and neoplastic disorders. It has been demonstrated that the laryngeal epithelium is more sensitive than the esophagus to injury by gastric reflux. Based on pH monitoring studies, up to 50 reflux episodes per day into the esophagus (below pH 4.0) are considered normal. In contrast, it has been shown experimentally that as few as three reflux episodes per week can produce severe laryngeal damage.  This increased sensitivity to damage may be an underlying cause of many diseases of the airway; however, the biological basis for this sensitivity to damage is not well understood. We propose that reflux-related laryngeal disease results when there is a breakdown in the defense mechanisms that normally protect against damage by corrosive refluxate.

One such defense mechanism that would protect the laryngeal epithelium against damage by LPR is carbonic anhydrase. Carbonic anhydrase (CA) catalyzes the reversible hydration of carbon dioxide, producing bicarbonate ions that are actively pumped into the extracellular space where they can neutralize refluxed gastric acid. By increasing pH, CA would also play an indirect role in reducing peptic activity. Eleven catalytically active isoenzymes have been isolated to date, each showing differences in activity, susceptibility to inhibitors, and tissue-specific distribution.  The esophagus has been shown to express CA-I to CA-IV in the epithelium. The presence of CA in the esophagus is physiologically important because endogenous bicarbonate secretion is capable of increasing the pH of gastroesophageal reflux– derived residual acid from 2.5 to almost neutrality.

Read more: Pepsin and Carbonic Anhydrase Isoenzyme III as Diagnostic Markers for Laryngopharyngeal Reflux Disease
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Nikki Johnston, PhD; John Knight, PhD; Peter W. Dettmar, PhD; Mark O. Lively, PhD; Jamie Koufman, MD

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