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Objectives <p>To assess the ability of the Reflux Symptom Index (RSI), Reflux Finding Score (RFS), and Reflux Symptom Score (RSS) to discriminate salivary pepsin exposure, and to explore relationships among latent clinical domains, adenoid obstruction, and diurnal pepsin burden in children.</p> Methods <p>In a prospective cross-sectional cohort of 84 children, RSI, RSS, and RFS were recorded. Standardized saliva samples (waking, post-lunch, post-dinner) were assayed for pepsin. ROC analyses evaluated clinical score discrimination across three positivity cutoffs <InlineEquation ID="IEq1"> <EquationSource Format="TEX">\(\text{16,50,75}ng/mL\)</EquationSource> </InlineEquation>. Exploratory factor analysis (EFA) reduced symptoms and signs into latent domains. Multidimensional k-means clustering defined diurnal rhythm phenotypes, and multivariable regression evaluated predictors of pepsin burden.</p> Results <p>Salivary pepsin was detected (&gt; 16&#xa0;ng/mL) in 71/84 children (84.5%). RSI, RFS, and RSS demonstrated near-chance discrimination across all cutoffs (AUC 0.46–0.60). Multidimensional clustering yielded diurnal profiles distinguished primarily by overall daily burden rather than isolated temporal peaks. Crucially, adenoid obstruction emerged as the predominant correlate for both continuous log-pepsin burden and high-load phenotype membership. In contrast, EFA-derived symptom domains and endoscopic signs (dominated by laryngeal edema) contributed limited independent predictive value.</p> Conclusions <p>Traditional clinical scores exhibit poor construct validity and are insufficient as standalone proxies for pediatric LPR exposure. Rhythm-aware phenotyping demonstrates that cumulative diurnal pepsin burden is strongly associated with structural adenoid obstruction, suggesting a potential pathophysiological interplay and highlighting the necessity for objective, continuous exposure metrics in pediatric research.</p> <p>Level of Evidence: 3.</p>

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Salivary pepsin exposure in children with upper-airway symptoms: limited discrimination by RSI/RFS/RSS and diurnal patterns

  • 期刊论文

  • 发表日期：

    2026年7月19日

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  • Chaofan Li,
  • Chaohua Wang,
  • Shaokun Huang,
  • Ying Zhang,
  • Fan Song,
  • Chun Zhang,
  • Xiaochun Li,
  • Manman Cheng,
  • Juan Ye,
  • Guanghao Yue,
  • Guoping Yin

摘要

Objectives

To assess the ability of the Reflux Symptom Index (RSI), Reflux Finding Score (RFS), and Reflux Symptom Score (RSS) to discriminate salivary pepsin exposure, and to explore relationships among latent clinical domains, adenoid obstruction, and diurnal pepsin burden in children.

Methods

In a prospective cross-sectional cohort of 84 children, RSI, RSS, and RFS were recorded. Standardized saliva samples (waking, post-lunch, post-dinner) were assayed for pepsin. ROC analyses evaluated clinical score discrimination across three positivity cutoffs \(\text{16,50,75}ng/mL\) . Exploratory factor analysis (EFA) reduced symptoms and signs into latent domains. Multidimensional k-means clustering defined diurnal rhythm phenotypes, and multivariable regression evaluated predictors of pepsin burden.

Results

Salivary pepsin was detected (> 16 ng/mL) in 71/84 children (84.5%). RSI, RFS, and RSS demonstrated near-chance discrimination across all cutoffs (AUC 0.46–0.60). Multidimensional clustering yielded diurnal profiles distinguished primarily by overall daily burden rather than isolated temporal peaks. Crucially, adenoid obstruction emerged as the predominant correlate for both continuous log-pepsin burden and high-load phenotype membership. In contrast, EFA-derived symptom domains and endoscopic signs (dominated by laryngeal edema) contributed limited independent predictive value.

Conclusions

Traditional clinical scores exhibit poor construct validity and are insufficient as standalone proxies for pediatric LPR exposure. Rhythm-aware phenotyping demonstrates that cumulative diurnal pepsin burden is strongly associated with structural adenoid obstruction, suggesting a potential pathophysiological interplay and highlighting the necessity for objective, continuous exposure metrics in pediatric research.

Level of Evidence: 3.