Clinical utility of salivary pepsin measurement in patients with proton pump inhibitor-refractory gastroesophageal reflux disease symptoms: a prospective comparative study

Abstract

Background

Salivary pepsin measurement has been reported to be useful for diagnosing gastroesophageal reflux disease (GERD). This study aimed to clarify the usefulness of salivary pepsin measurement in patients with proton pump inhibitor (PPI)-refractory GERD symptoms without erosive esophagitis.

Methods

One hundred and two patients were included. Over seven days after terminating PPI treatment, all patients underwent a 24-h pH-impedance test and salivary pepsin measurement. In patients whose main symptoms included laryngopharyngeal symptoms, a hypopharyngeal multichannel intraluminal impedance (HMII) test was performed, whereas in other patients, a conventional combined multichannel intraluminal impedance-pH (MII-pH) test was performed. In the HMII tests, patients were divided into abnormal proximal exposure (APE) and non-APE groups. Salivary pepsin concentrations were compared according to acid exposure time (AET) values and were also compared between the APE and non-APE groups.

Results

The median salivary pepsin concentration in patients with AET > 6% was significantly higher than that in patients with AET ≤ 6% (345.0 [170.0–469.3] ng/mL vs. 120.0 [97.0–290.1] ng/mL, p < 0.01). The sensitivity, specificity, positive predictive value, and negative predictive value of a positive test (> 109 ng/mL) to diagnose patients with AET > 6% were 75.0%, 51.3%, 32.1%, and 86.9%, respectively. There was no significant difference between concentrations in the APE group and concentrations in the non-APE group.

Conclusions

In patients with PPI-refractory nonerosive reflux disease, salivary pepsin measurement may help diagnose patients who have conclusive evidence of reflux, whereas it is not adequate for identifying patients with APE.

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Abbreviations

GERD:

Gastroesophageal reflux disease

NERD:

Nonerosive reflux disease

FH:

Functional heartburn

RH:

Reflux hypersensitivity

AET:

Acid exposure time

MII-pH:

Combined multichannel intraluminal impedance-pH

HMII:

Hypopharyngeal multichannel intraluminal impedance

PPI:

Proton pump inhibitor

LPR:

Laryngopharyngeal reflux

APE:

Abnormal proximal exposure

FCR:

Full column reflux

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Acknowledgements

We thank Atsuko Kikuchi and Mai Fujie for their help on 24-h pH impedance test.

Funding

This work was supported by JSPS KAKENHI Grant No. 18K09367.

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Affiliations

Authors

Contributions

TM and TS designed the study, conducted the experiment, collected data, analyzed and interpreted data, and wrote the manuscript. TM, AM, TS, and TH designed the study, analyzed, and interpreted data, assisted in writing the manuscript. YS, SK, HI, KI, KO, NA, DM, and TN assisted in conducting the experiment and collecting data. TO, YO, and NK assisted in interpreting data and writing the manuscript. All authors approved the final version of the manuscript.

Corresponding author

Correspondence to Tomoaki Matsumura.

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Ethical Statement

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1964 and later versions. Informed consent or substitute for it was obtained from all patients for being included in the study.

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The authors indicated no potential conflicts of interest.

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Matsumura, T., Arai, M., Suzuki, T. et al. Clinical utility of salivary pepsin measurement in patients with proton pump inhibitor-refractory gastroesophageal reflux disease symptoms: a prospective comparative study. Esophagus 17, 339–347 (2020). https://doi.org/10.1007/s10388-020-00714-z

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Keywords

  • GERD
  • LPR
  • Salivary pepsin
  • Ppi-refractory GERD
  • NERD