Pepsin detection in patients with laryngopharyngeal reflux before and after fundoplication

Wassenaar, Eelco B.; Johnston, Nikki; Meratı, Albert L.; Montenovo, Martin I.; Petersen, Rebecca P.; Tatum, Roger P.; Pellegrini, Carlos A.; Oelschlager, Brant K.

doi:10.1007/s00464-011-1813-z

Cited by 49 publications

(36 citation statements)

References 22 publications

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“…The presence of pepsin in the laryngopharynx has also been shown to correlate with reflux events [17] and has been found in the laryngeal epithelial mucosa of patients with reflux-attributed laryngeal disease [18,19]. Pepsin has been identified in the sputum and bronchoalveolar lavage fluid of patients with chronic cough and LPR [6,20], and it has been used to indicate aspiration in patients with lung allografts [21] and the effectiveness of anti-reflux surgery [22]. Salivary pepsin has a moderate sensitivity and specificity for the diagnosis of gastrooesophageal reflux disease in patients with heartburn [23], and its association with scores obtained by clinical diagnostic tools such as the RSI and RFS has been investigated only in smaller studies to date [24,25].…”

Section: Introductionmentioning

confidence: 97%

Detecting laryngopharyngeal reflux in patients with upper airways symptoms: Symptoms, signs or salivary pepsin?

Spyridoulias

Lillie

Vyas

et al. 2015

Respiratory Medicine

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Section: Introductionmentioning

confidence: 97%

Detecting laryngopharyngeal reflux in patients with upper airways symptoms: Symptoms, signs or salivary pepsin?

Spyridoulias

Lillie

Vyas

et al. 2015

Respiratory Medicine

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“…Moreover, some investigators consider detection of a pH in the pharynx less than 4.0 more than 1% of the study time to be pathological [13], whereas in a large population of normal subjects a pH less than 4.0 may be occasionally observed [14]. Pepsin, a protease secreted by gastric chief cells, has clearly been shown to be a component of the refluxate that is capable of extending supraesophageally to the larynx [15]. Pepsin is active at acidic pH (≤4.0), while in less acidic environment the catalytic activity of pepsin gradually decreases with increasing pH until it is fully denatured and irreversibly inactivated at pH 8.0 [16].…”

Section: Introductionmentioning

confidence: 99%

The In Vitro Effect of Acidic-Pepsin on Nuclear Factor KappaB Activation and Its Related Oncogenic Effect on Normal Human Hypopharyngeal Cells

Sasaki¹,

Toman²,

Vageli³

2016

PLoS ONE

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BackgroundExtra-esophageal carcinogenesis has been widely discussed in relation to the chronic effects of laryngopharyngeal reflux and most prominently with pepsin historically central to this discussion. With refluxate known to include gastric (pepsin) and duodenal (bile) fluids, we recently demonstrated the mechanistic role of NF-κB in mediating the preneoplastic effects of acidic-bile. However, the role of pepsin in promoting hypopharyngeal premalignant events remains historically unclear. Here, we investigate the in vitro effect of acidic-pepsin on the NF-κB oncogenic pathway to better define its potential role in hypopharyngeal neoplasia.MethodsHuman hypopharyngeal primary cells (HHPC) and keratinocytes (HHK) were repetitively exposed to physiologic pepsin concentrations (0.1 mg/ml) at pH 4.0, 5.0 and 7.0. Cellular localization of phospho-NF-κB and bcl-2 was determined using immunofluorescence and western blotting. NF-κB transcriptional activity was tested by luc reporter and qPCR. Analysis of DNA content of pepsin treated HHK and HHPC was performed using Fluorescence-activated-cell sorting assay. To explore a possible dose related effect, pepsin concentration was reduced from 0.1 to 0.05 and 0.01 mg/ml.ResultsAt physiologic concentration, acidic-pepsin (0.1 mg/ml at pH 4.0) is lethal to most normal hypopharyngeal cells. However, in surviving cells, no NF-κB transcriptional activity is noted. Acidic-pepsin fails to activate the NF-κB or bcl-2, TNF-α, EGFR, STAT3, and wnt5α but increases the Tp53 mRNAs, in both HHPC and HHK. Weakly acidic-pepsin (pH 5.0) and neutral-pepsin (pH 7.0) induce mild activation of NF-κB with increase in TNF-α mRNAs, without oncogenic transcriptional activity. Lower concentrations of pepsin at varying pH do not produce NF-κB activity or transcriptional activation of the analyzed genes.ConclusionOur findings in vitro do not support the role of acidic-pepsin in NF-κB related hypopharyngeal carcinogenesis.

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“…Wassenaar et al 2011 [14] introduced a new approach to preoperative evaluation. While most of the studies use classical evaluation with dual-probe 24 h-esophageal pHmetry, upper endoscopy, laryngoscopy, in this study, patients were additionally evaluated with laryngeal pepsin measured by western blotting in sputum and posterior laryngeal biopsies.…”

Section: Resultsmentioning

confidence: 99%

Impact of Laparoscopic Fundoplication for the Treatment of Laryngopharyngeal Reflux: Review of the Literature

Mazzini

Gurski

2012

International Journal of Otolaryngology

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Laryngopharyngeal reflux (LPR) is part of the so-called extraesophageal manifestations of gastroesophageal reflux disease (GERD). It is presented by unspecific symptoms and signs and is believed to be caused by the reflux of gastric content to the proximal esophagus and larynx. However, evidence considering the role of the antireflux surgery for LPR has failed to demonstrate results comparable to those for GERD. The aim of this paper is to review the current literature regarding the impact of laparoscopic fundoplication for the treatment of LPR.

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Pepsin detection in patients with laryngopharyngeal reflux before and after fundoplication

Abstract: Pepsin is often found on laryngeal epithelial biopsy and in sputum of patients with pH-test-proven GERD and symptoms of LPR. ARS improves symptoms and clears pepsin from the upper airway. Detection of pepsin improves diagnostic accuracy in patients with LPR.

Cited by 49 publications

References 22 publications

Detecting laryngopharyngeal reflux in patients with upper airways symptoms: Symptoms, signs or salivary pepsin?

Detecting laryngopharyngeal reflux in patients with upper airways symptoms: Symptoms, signs or salivary pepsin?

The In Vitro Effect of Acidic-Pepsin on Nuclear Factor KappaB Activation and Its Related Oncogenic Effect on Normal Human Hypopharyngeal Cells

Impact of Laparoscopic Fundoplication for the Treatment of Laryngopharyngeal Reflux: Review of the Literature

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