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Salivary pepsin exposure in children with upper-airway symptoms: limited discrimination by RSI/RFS/RSS and diurnal
Chaofan Li1,2, Chaohua Wang1,2, Shaokun Huang1,2
1Department of Otolaryngology, Affiliated Hospital of Qinghai University, Xining, Qinghai Province, People's Republic of China.
Insights
Traditional clinical scores poorly identify pediatric reflux symptoms. Adenoid obstruction, not symptom scores, strongly correlates with daily pepsin exposure in children, indicating a need for better diagnostic tools.
Area of Science:
- Otolaryngology
- Pediatric Gastroenterology
- Biomarkers
Background:
- Pediatric laryngopharyngeal reflux (LPR) diagnosis relies on subjective symptom scores.
- Objective measures of pepsin exposure in children are lacking.
- The relationship between clinical symptoms, adenoid obstruction, and pepsin burden is unclear.
Purpose of the Study:
- To evaluate the diagnostic accuracy of Reflux Symptom Index (RSI), Reflux Finding Score (RFS), and Reflux Symptom Score (RSS) for salivary pepsin exposure in children.
- To explore associations between clinical symptom domains, adenoid obstruction, and diurnal pepsin burden.
- To identify phenotypes of diurnal pepsin rhythm in children.
Main Methods:
- Prospective cross-sectional study of 84 children.
- Salivary pepsin levels measured at waking, post-lunch, and post-dinner.
- Receiver operating characteristic (ROC) analyses for clinical score discrimination.
- Exploratory factor analysis (EFA) and k-means clustering for symptom/sign analysis and diurnal phenotyping.
- Multivariable regression to identify predictors of pepsin burden.
Main Results:
- Salivary pepsin detected in 84.5% of children.
- RSI, RFS, and RSS showed poor discrimination (AUC 0.46-0.60).
- Adenoid obstruction was the primary correlate of pepsin burden and high-load phenotypes.
- EFA-derived symptom domains and endoscopic findings had limited predictive value.
Conclusions:
- Current clinical scores lack construct validity for pediatric LPR and are insufficient proxies for pepsin exposure.
- Cumulative diurnal pepsin burden is significantly associated with adenoid obstruction.
- Objective, continuous exposure metrics are essential for pediatric LPR research.
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 [Formula: see text]. 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.
