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Laryngoscope. 2005 Jul;115(7):1230-8.

Laryngopharyngeal reflux: prospective cohort study evaluating optimal dose of proton-pump inhibitor therapy and pretherapy predictors of response.

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  • 1Department of Gastroenterology and Hepatology, Center for Swallowing and Esophageal Disorders, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA.



Laryngopharyngeal reflux (LPR) is frequently treated with empiric proton-pump inhibitors (PPI), but the optimal dosing and duration is unknown. We performed an open label prospective cohort study to evaluate whether twice-daily (BID) PPI is more effective than once-daily (QD) PPI for the treatment of LPR.


Patients diagnosed with LPR based on ear, nose, and throat (ENT) symptoms and laryngoscopy findings were enrolled. Questionnaire assessed demographics, ENT symptoms, symptom severity, and exposure to other potential laryngeal irritants. Esophageal manometry, ambulatory 24-hour pH monitoring, and upper gastrointestinal endoscopy were performed before initiation of therapy. Patients were consecutively assigned to three groups: BID PPI (lansoprazole 30 mg BID), BID PPI + H2 receptor antagonist (H2RA; omeprazole 20 mg BID + ranitidine 300 mg each night), or QD PPI (esomeprazole 40 mg QD). Greater than 50% primary symptom improvement from baseline defined symptom response. At 2 month follow-up, the same PPI dose was continued for responders, and PPIs were doubled for nonresponders for an additional 2 months. Repeat symptom assessment and laryngoscopy performed at 4 month follow-up.


Eighty-five patients were enrolled (median age 49 years, interquartile range 44.0 - 65.0; 76% white; 34% male). Treatment groups were BID PPI for 30 patients, BID PPI + H2RA for 30 patients, and QD PPI for 25 patients. RESPONSE TO THERAPY: At 2 months, BID response occurred among 15 of 30 (50%) patients, BID + H2RA for 15 of 30 (50%), and QD for 7 of 25 (28%) (P = .03). No statistical difference found between the two BID PPI groups with and without H2RA. Among the QD group nonresponders, 7 of 13 (54%) achieved symptom response with additional 2 months of BID dosing. At 4 month follow-up, an additional 22% of responses were obtained from the two BID groups (43/60, 72%). The overall response rate for all three groups was 70% (54/77). PREDICTORS OF OUTCOME: Pretherapy interarytenoid mucosa and true vocal folds abnormalities were associated with twofold increase in symptom response (odds ratio 1.99 and 1.96, respectively, P = .017).


BID PPI appears to be more effective than QD PPI in achieving clinical symptom response in suspected LPR. More response was achieved at 4 months compared with 2 months. Therefore, aggressive acid suppression with BID PPI for at least 4 months is warranted for treatment of LPR.

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