Background: Patients with suspected laryngopharyngeal reflux (LPR) present a diagnostic challenge as traditional esophageal reflux criteria may not correlate with pharyngeal reflux events. Mean nocturnal baseline impedance (MNBI) is a recognized measure of esophageal mucosal integrity that correlates with overall reflux burden. However, a metric that considers the mucosal integrity gradient in the proximal-mid esophagus may better elucidate the relationship between MNBI and pharyngeal reflux.

Aim: To identify and evaluate the novel metric of proximal MNBI gradient and its relationship to pharyngeal reflux in patients with suspected LPR.

Methods: Consecutive adults with suspected LPR who were referred for combined hypopharyngeal-esophageal multichannel intraluminal pH-impedance study (HEMII-pH) and high-resolution impedance-manometry (HRiM) from 8/2020 to 11/2021 were enrolled. MNBI was calculated by selecting three 10-minute time periods (approx. 1AM, 2AM, 3AM), computing the mean baseline during those time periods, and then manually calculating the mean of the three measurements. MNBI gradient was defined as the proximal esophageal MNBI from the electrode pair located within 1 cm of the upper esophageal sphincter (UES) divided by that located 9 cm below the UES (Figure 1). Spearman correlation was used to analyze univariate associations between pharyngeal reflux and HEMII-pH/HRiM metrics. General linear regression was used to control for potential confounders.

Results: 74 patients (mean age 55.1±15.9 years, 63.5% (n=47) female, mean body mass index (BMI) 27.1±6.46 kg/m²) were enrolled. The mean and median number of pharyngeal reflux events were 2.18±3.74 and 1 [25-75%: 0-3], respectively. Pharyngeal reflux events correlated positively with increased acid exposure time (R=0.1656, p=0.0168), total (R=0.3484, p<0.0001) and proximal reflux events (R=0.4737, p<0.0001) on HEMII-pH, but negatively with complete bolus transit (R=-0.4344, p=0.0081) on HRiM. Higher proximal MNBI gradient was associated with greater pharyngeal reflux events (R=0.3929, p=0.0122), Dominant Symptom Index (DSI) score (R=0.3571, p=0.0300), and cough symptoms (Yes: 1.885 (SD 1.5) vs No: 1.190 (SD 0.94), p=0.0195). On multivariate analysis, after controlling for age, sex, and BMI, a higher proximal MNBI gradient remained independently associated with a greater number of pharyngeal reflux events (β=1.075, p=0.0416, Table 1).

Conclusion: Proximal MNBI gradient is a novel metric that may help to predict pharyngeal reflux in patients with suspected LPR. The use of a mucosal impedance gradient in the proximal-mid esophagus may underscore the potential of other technologies such as endoscopic assessment of mucosal impedance in the evaluation of extraesophageal symptoms.

Figure 1. The hypopharyngeal-esophageal multichannel intraluminal impedance and pH catheter contains 6 impedance electrodes pairs, divided into pharyngeal (3 and 1 cm above UES and 1 cm below UES), proximal esophageal (1, 3 and 5 cm below UES), and distal esophageal (9, 11, and 13 cm below UES).

Table 1. On multivariate analysis, a higher proximal mean nocturnal baseline impedance (MNBI) gradient remained independently associated with a greater number of pharyngeal reflux events even after controlling for confounders.
BMI=body mass index

Thomas Carroll

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