A Randomized, Double-blind, Placebo-controlled Study of Dexlansoprazole to Treat Laryngopharyngeal Reflux and Lingual Tonsil Hypertrophy

BACKGROUND AND SIGNIFICANCE:

Detail: The backflow of gastric contents into the esophagus occurs in healthy people to a limited extent.[1] When the refluxed material transcends the upper esophageal sphincter and enters the laryngopharynx on a chronic basis, it is termed laryngopharyngeal reflux (LPR). LPR typically manifests as dysphonia, globus sensation, chronic cough, and throat irritation. Recent studies suggest that untreated LPR may be a cause of lingual tonsil hypertrophy (LTH), [2,3] which itself has been implicated as a contributing factor in obstructive sleep apnea-hypopnea syndrome (OSAHS).[4-6] Lingual tonsil tissue (LTT) is present to a variable degree in most individuals and tends to regress with age. Although standardized parameters for defining LTH have yet to be established, a recent study by Friedman et al [7] demonstrated that on average subjects with LPR, OSAHS, or both diseases had significantly thicker LTT on CT imaging than patients without either disease. Del Gaudio and coworkers [2] identified a trend between increasing severity of LTH and the frequency of reflux events, while Mamede et al [3] found a positive correlation between reflux symptoms and the degree of LTH.

LTH in the setting of LPR is thought to result from the edema and inflammation brought about by chronic exposure of the tissues to the refluxed acid. The resulting thickened and inflamed LTT may narrow the retrolingual airway, increasing the likelihood of airway obstruction and apneic events. Theoretically, increases in negative intrathoracic pressure secondary to the obstruction may, in turn, facilitate further LPR.

While the treatment of reflux has been shown to decrease indices of OSAHS severity in some patients, [8-10] a direct causal relationship between LPR and OSAHS has not been proven. Similarly, more evidence is necessary to elucidate the exact relationship between LPR and LTH. No study to date has investigated whether treatment of LPR reduces LTH. The investigators hypothesize that adequate treatment of LPR using a PPI in patients with LTH will result in a significant reduction in LTT thickness as well as improvement in OSAHS symptoms, if present. The proposed study is a randomized, double-blind, controlled trial to determine whether control of LPR reduces LTH and, as a corollary, improves OSAHS symptoms. Control of LPR will be determined by 24-hour oropharyngeal pH monitoring [11], and LTH will be measured on CT. While the length of time required for LTH regression to occur is not currently known, Reichel et al have found that 3 months of PPI therapy are typically necessary before improvement in LPR is seen. [12] Similarly, a study by Park et al showed a significantly greater rate of improvement or resolution of LPR symptoms when treatment with a PPI was for longer than 2 months. [13] PRELIMINARY STUDIES Preliminary Studies: In a previous study, the investigators utilized axial and sagittal CT images of the tongue base to measure LTT in patients with LPR, OSAHS, both conditions, or neither disease. The investigators found that patients with LPR, OSAHS, or LPR+OSAHS had significantly thicker LTT than patients without LPR or OSAHS. This study was presented at the 2009 Annual Meeting of the American Academy of Otolaryngology-Head and Neck Surgery and was published in the April 2010 issue of the journal Otolaryngology-Head and Neck Surgery.

RESEARCH DESIGN AND METHODS: