Pepsin in saliva as a biomarker for oropharyngeal reflux compared with 24-hour esophageal impedance/pH monitoring in pediatric patients

J. E. Fortunato; R. B. D'Agostino; M. O. Lively

doi:10.1111/nmo.12936

Pepsin in saliva as a biomarker for oropharyngeal reflux compared with 24-hour esophageal impedance/pH monitoring in pediatric patients

J. E. Fortunato^*, R. B. D'Agostino, M. O. Lively

^*Corresponding author for this work

Pediatrics

Research output: Contribution to journal › Article › peer-review

43 Scopus citations

Abstract

Background: Pepsin in saliva is a proposed biomarker for oropharyngeal reflux. Pepsin may be prevalent in saliva from subjects with gastro-esophageal reflux and may correlate with proximal reflux by intraluminal impedance/pH monitoring (MII/pH). Methods: Patients (3 days to 17.6 years, n=90) undergoing 24-hour MII/pH monitoring and asymptomatic controls (2 months to 13.7 years, n=43) were included. Salivary pepsin was determined using a pepsin enzyme-linked immunosorbent assay. Eight saliva samples were collected from patients undergoing 24-hr MII/pH: (i) before catheter placement, (ii) before and 30 minutes after each of three meals, and (iii) upon awakening. One sample was collected from each control. Key Results: In MII/pH subjects, 85.6% (77/90) had at least one pepsin-positive sample compared with 9.3% (4/43) in controls. The range of pepsin observed in individual subjects varied widely over 24 hours. The average pepsin concentration in all samples obtained within 2 hours following the most recent reflux event was 30.7±135 ng/mL, decreasing to 16.5±39.1 ng/mL in samples collected more than 2 hours later. The frequency of pepsin-positive samples correlated significantly with symptom index (r_S=0.332, P=.0014), proximal (r_S=0.340, P=.0010), and distal (r_S=0.272, P=.0095) MII events. Conclusions & Inferences: Concentration of salivary pepsin may not be an accurate measure of severity of reflux because of the wide range observed in individuals over 24 hours. Saliva samples must be obtained soon after a reflux event. Defining a regimen for optimal saliva collection may help to achieve the goal of using salivary pepsin as a biomarker for oropharyngeal reflux. Clinical Trial registry: NCT01091805.

Original language	English (US)
Article number	e12936
Journal	Neurogastroenterology and Motility
Volume	29
Issue number	2
DOIs	https://doi.org/10.1111/nmo.12936
State	Published - Feb 1 2017

Funding

No funding declared. The authors thank Ms. Koulnara Kourman for her expert performance of the pepsin ELISA, Ms. Anya Brown for her clinical coordination and database support, and Ms. Candice Shumate for her support in the endoscopy clinic during the study. This work was supported by an Investigator Initiated grant sponsored by Takeda Pharmaceuticals – MSA-NC-DEX-108. The authors had full access to all data collected during the study. The sponsors had no role in interpretation of the results or in writing the manuscript.

Keywords

gastro-esophageal reflux
multichannel intraluminal impedance/pH monitoring
oropharyngeal pepsin
oropharyngeal reflux
pepsin
saliva

ASJC Scopus subject areas

Endocrine and Autonomic Systems
Gastroenterology
Physiology

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10.1111/nmo.12936

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title = "Pepsin in saliva as a biomarker for oropharyngeal reflux compared with 24-hour esophageal impedance/pH monitoring in pediatric patients",

abstract = "Background: Pepsin in saliva is a proposed biomarker for oropharyngeal reflux. Pepsin may be prevalent in saliva from subjects with gastro-esophageal reflux and may correlate with proximal reflux by intraluminal impedance/pH monitoring (MII/pH). Methods: Patients (3 days to 17.6 years, n=90) undergoing 24-hour MII/pH monitoring and asymptomatic controls (2 months to 13.7 years, n=43) were included. Salivary pepsin was determined using a pepsin enzyme-linked immunosorbent assay. Eight saliva samples were collected from patients undergoing 24-hr MII/pH: (i) before catheter placement, (ii) before and 30 minutes after each of three meals, and (iii) upon awakening. One sample was collected from each control. Key Results: In MII/pH subjects, 85.6% (77/90) had at least one pepsin-positive sample compared with 9.3% (4/43) in controls. The range of pepsin observed in individual subjects varied widely over 24 hours. The average pepsin concentration in all samples obtained within 2 hours following the most recent reflux event was 30.7±135 ng/mL, decreasing to 16.5±39.1 ng/mL in samples collected more than 2 hours later. The frequency of pepsin-positive samples correlated significantly with symptom index (rS=0.332, P=.0014), proximal (rS=0.340, P=.0010), and distal (rS=0.272, P=.0095) MII events. Conclusions & Inferences: Concentration of salivary pepsin may not be an accurate measure of severity of reflux because of the wide range observed in individuals over 24 hours. Saliva samples must be obtained soon after a reflux event. Defining a regimen for optimal saliva collection may help to achieve the goal of using salivary pepsin as a biomarker for oropharyngeal reflux. Clinical Trial registry: NCT01091805.",

keywords = "gastro-esophageal reflux, multichannel intraluminal impedance/pH monitoring, oropharyngeal pepsin, oropharyngeal reflux, pepsin, saliva",

author = "Fortunato, {J. E.} and D'Agostino, {R. B.} and Lively, {M. O.}",

note = "Funding Information: No funding declared. The authors thank Ms. Koulnara Kourman for her expert performance of the pepsin ELISA, Ms. Anya Brown for her clinical coordination and database support, and Ms. Candice Shumate for her support in the endoscopy clinic during the study. This work was supported by an Investigator Initiated grant sponsored by Takeda Pharmaceuticals – MSA-NC-DEX-108. The authors had full access to all data collected during the study. The sponsors had no role in interpretation of the results or in writing the manuscript. Publisher Copyright: {\textcopyright} 2016 John Wiley & Sons Ltd",

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doi = "10.1111/nmo.12936",

language = "English (US)",

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T1 - Pepsin in saliva as a biomarker for oropharyngeal reflux compared with 24-hour esophageal impedance/pH monitoring in pediatric patients

AU - Fortunato, J. E.

AU - D'Agostino, R. B.

AU - Lively, M. O.

N1 - Funding Information: No funding declared. The authors thank Ms. Koulnara Kourman for her expert performance of the pepsin ELISA, Ms. Anya Brown for her clinical coordination and database support, and Ms. Candice Shumate for her support in the endoscopy clinic during the study. This work was supported by an Investigator Initiated grant sponsored by Takeda Pharmaceuticals – MSA-NC-DEX-108. The authors had full access to all data collected during the study. The sponsors had no role in interpretation of the results or in writing the manuscript. Publisher Copyright: © 2016 John Wiley & Sons Ltd

PY - 2017/2/1

Y1 - 2017/2/1

N2 - Background: Pepsin in saliva is a proposed biomarker for oropharyngeal reflux. Pepsin may be prevalent in saliva from subjects with gastro-esophageal reflux and may correlate with proximal reflux by intraluminal impedance/pH monitoring (MII/pH). Methods: Patients (3 days to 17.6 years, n=90) undergoing 24-hour MII/pH monitoring and asymptomatic controls (2 months to 13.7 years, n=43) were included. Salivary pepsin was determined using a pepsin enzyme-linked immunosorbent assay. Eight saliva samples were collected from patients undergoing 24-hr MII/pH: (i) before catheter placement, (ii) before and 30 minutes after each of three meals, and (iii) upon awakening. One sample was collected from each control. Key Results: In MII/pH subjects, 85.6% (77/90) had at least one pepsin-positive sample compared with 9.3% (4/43) in controls. The range of pepsin observed in individual subjects varied widely over 24 hours. The average pepsin concentration in all samples obtained within 2 hours following the most recent reflux event was 30.7±135 ng/mL, decreasing to 16.5±39.1 ng/mL in samples collected more than 2 hours later. The frequency of pepsin-positive samples correlated significantly with symptom index (rS=0.332, P=.0014), proximal (rS=0.340, P=.0010), and distal (rS=0.272, P=.0095) MII events. Conclusions & Inferences: Concentration of salivary pepsin may not be an accurate measure of severity of reflux because of the wide range observed in individuals over 24 hours. Saliva samples must be obtained soon after a reflux event. Defining a regimen for optimal saliva collection may help to achieve the goal of using salivary pepsin as a biomarker for oropharyngeal reflux. Clinical Trial registry: NCT01091805.

AB - Background: Pepsin in saliva is a proposed biomarker for oropharyngeal reflux. Pepsin may be prevalent in saliva from subjects with gastro-esophageal reflux and may correlate with proximal reflux by intraluminal impedance/pH monitoring (MII/pH). Methods: Patients (3 days to 17.6 years, n=90) undergoing 24-hour MII/pH monitoring and asymptomatic controls (2 months to 13.7 years, n=43) were included. Salivary pepsin was determined using a pepsin enzyme-linked immunosorbent assay. Eight saliva samples were collected from patients undergoing 24-hr MII/pH: (i) before catheter placement, (ii) before and 30 minutes after each of three meals, and (iii) upon awakening. One sample was collected from each control. Key Results: In MII/pH subjects, 85.6% (77/90) had at least one pepsin-positive sample compared with 9.3% (4/43) in controls. The range of pepsin observed in individual subjects varied widely over 24 hours. The average pepsin concentration in all samples obtained within 2 hours following the most recent reflux event was 30.7±135 ng/mL, decreasing to 16.5±39.1 ng/mL in samples collected more than 2 hours later. The frequency of pepsin-positive samples correlated significantly with symptom index (rS=0.332, P=.0014), proximal (rS=0.340, P=.0010), and distal (rS=0.272, P=.0095) MII events. Conclusions & Inferences: Concentration of salivary pepsin may not be an accurate measure of severity of reflux because of the wide range observed in individuals over 24 hours. Saliva samples must be obtained soon after a reflux event. Defining a regimen for optimal saliva collection may help to achieve the goal of using salivary pepsin as a biomarker for oropharyngeal reflux. Clinical Trial registry: NCT01091805.

KW - gastro-esophageal reflux

KW - multichannel intraluminal impedance/pH monitoring

KW - oropharyngeal pepsin

KW - oropharyngeal reflux

KW - pepsin

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Pepsin in saliva as a biomarker for oropharyngeal reflux compared with 24-hour esophageal impedance/pH monitoring in pediatric patients

Abstract

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