In otolaryngologic practice, recognition of many of the clinical manifestations of laryngopharyngeal reflux (LPR) have gained acceptance; however, the prevalence of otolaryngologic and respiratory disorders caused by LPR remains unknown. In part, this appears to be because currently used diagnostics for LPR often rely on testing methods and normative standards that were established for the diagnosis of classic gastroesophageal reflux disease (GERD), which may not be appropriate for use in diagnosing LPR.
Ambulatory 24-hour double-probe (simultaneous esophageal and pharyngeal) pH monitoring (pH-metry) is the current gold standard for diagnosis of LPR, but it is far from being an ideal test. First, the reported sensitivity of pH-metry is only 50% to 80%. Second, approximately 12% of otolaryngologic patients cannot tolerate the procedure. Third, dietary modifications (to standardize the test) may lead to false-negative pH studies. And finally, pH-metry is expensive and has limited availability. Thus,
there appears to be a need for a sensitive, noninvasive, and inexpensive diagnostic test for LPR.
Pepsinogens belong to a family of aspartic proteinases and are produced primarily by chief cells within the gastric fundus. In the acidic environment of the stomach, pepsinogen is activated by HCL (acid). Pepsin plays a major role in the development of many reflux-related disorders.
Gastroesophageal reflux always contains pepsin, but not all reflux occurs below pH 4.0. Thus, with use of traditional gastroenterology standards for pH-metry, significant LPR may be under diagnosed. Indeed, pepsin exhibits enzymatic activity at pH levels well above, and it is only irreversibly inactivated at a pH greater than 6.5. Thus, a patient could conceivably have a negative pH study (no reflux events pH ≤ 4) but might still have significant LPR-related disease. We have previously reported that the laryngeal epithelium is far more sensitive to damage by pepsin in the presence of acid than is esophageal epithelium, and that may help explain why the patterns of reflux, reflux mechanisms, and clinical manifestations of LPR and GERD are so different.
We postulated that measurement of pepsin in airway secretions might provide a sensitive diagnostic marker for LPR, and furthermore, because pepsin is a large molecule, that it might be detected in airway secretions long after gastric reflux had occurred, making it a good diagnostic marker (U.S. Patent No. 5,879,897). Our strategy was to develop an enzyme-linked immunosorbent assay (ELISA) to detect pepsin and then to test its diagnostic sensitivity and specificity in a clinical setting.
John Knight, PhD; Mark O. Lively, PhD; Nikki Johnston, PhD; Peter W. Dettmar, PhD; Jamie A. Koufman, MD