BACKGROUND: Persistent symptoms on acid suppressive therapy are due to either acid or nonacid gastroesophageal reflux (GER) episodes or are not related to reflux. AIM: To compare physical and chemical characteristics of GER episodes associated with symptoms in patients on acid suppressive therapy. METHODS: Patients with persistent symptoms on acid suppressive therapy underwent combined impedance-pH monitoring. Reflux episodes were classified as acid if nadir pH was <4.0, and nonacid if it remained at ≥4.0, separated into liquid-only or mixed (liquid-gas), and considered to reach the proximal esophagus if liquid was present 15 cm above the lower esophageal sphincter (LES). Reflux episodes were considered symptomatic if patients recorded a symptom within 5 min after the reflux episode. Risk factors of symptomatic reflux episodes were identified using multivariable generalized estimating equations (GEEs). RESULTS: One hundred twenty patients (85 women, median age 54 yr, range 18-85 yr) recorded 3,547 reflux episodes (84.3% nonacid, 50.6% mixed), of which 468 (13.2%) were symptomatic. Based on multivariable GEE analysis with episode-level symptom status (symptomatic vs nonsymptomatic) as the outcome variable, reflux episode acidity was not significantly associated with symptoms (P = 0.40). Mixed reflux episodes were significantly associated with symptoms relative to liquid-only episodes (odds ratio [OR] 1.49, 95% confidence interval [CI] 1.19-1.87, P = 0.0005), as were reflux episodes reaching the proximal esophagus compared with those reaching the distal esophagus only (OR 1.28, 95% CI 1.06-1.55, P = 0.012). CONCLUSION: The majority of reflux episodes on acid suppressive therapy are asymptomatic. Reflux episodes extending proximally and having a mixed (liquid-gas) composition are significantly associated with symptoms, irrespective of whether pH is acid (<4) or nonacid (≥4).
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