ESOPHAGEAL ACID AND SYMPTOM FREQUENCY IN GERD PHENOTYPES: A QUADRANT-BASED ANALYSIS OF SUBJECT-LEVEL VARIATION
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Background
The Lyon Consensus identified distinct phenotypes of symptomatic GERD subjects: NERD, reflux hypersensitivity, and functional heartburn; however, the Consensus did not describe a relationship between esophageal acid exposure and symptom frequency.
Objective
The present analyses aim to examine this relationship in ways that capture the variation among individual GERD subjects.
Design
Records of symptoms and 24-hour esophageal pH from 60 subjects with a normal upper endoscopy were grouped using the Lyon criteria for the three phenotypes of GERD (20 subjects per phenotype). Interval esophageal acidity was calculated before each symptom from 24-hour pH recordings. The value for symptom frequency was plotted versus the corresponding value for esophageal acid for each subject on a graph divided into quadrants based on the median value for symptom frequency and esophageal acid from all 60 subjects. Thus, each subject was categorized as esophageal acid: symptom frequency as high: high; high: low; low: high or low: low.
Results
Subjects were distributed among all 4 quadrants, and each quadrant tended to cluster a specific Lyon Consensus phenotype (Chi-Square P=0.00018). There was a significant discordant relationship between esophageal acid and symptom frequency in 63% of subjects (high:low or low:high; binomial probability = 0.0123).
Conclusions
The quadrant classification captures the essential variation in GERD subjects, aligns with phenotype groupings, reflects symptom burden (which phenotypes ignore), and maps more directly to possible treatment decisions. Given its simplicity and interpretability, a quadrant-based diagnosis and subsequent treatment choice may provide a pragmatic, evidence-based approach in routine clinical care.
