J. Liu, Yang Fu
We read with interest the study by Chan et al., which demonstrates that Asian patients undergoing pH-impedance monitoring for suspected gastro-oesophageal reflux disease (GERD) report higher global symptom severity (GSS) despite lower acid exposure time (AET) compared with US patients [1]. The authors appropriately conclude that region-specific diagnostic thresholds may be warranted, supporting an Asian AET threshold of > 4% for conclusive GERD and classifying those with AET < 4% plus supportive criteria as inconclusive GERD. These findings provide important evidence that the uniform thresholds proposed in the Lyon Consensus 2.0 may not fully capture the Asian reflux phenotype [2]. We propose that this discussion should extend beyond diagnostic classification into clinical management. The key question is not only whether diagnostic thresholds should be lower in Asian patients, but how adjusted thresholds should guide treatment decisions. Lowering the AET threshold from 6% to 4% increased the relative diagnostic yield by 21% in the Asian cohort [1]. This is diagnostically important, but its therapeutic meaning remains to be defined. Increased diagnostic sensitivity should not automatically translate into intensified acid suppression or invasive anti-reflux management. The data presented by Chan et al. suggest distinct phenotypes within the Asian cohort, but also caution against treating any single metric as decisive. Asian patients had higher total reflux episodes (TRE; 55.4 vs. 46.4) and were more likely to present with regurgitation-dominant symptoms (59.9% vs. 19.9%), while having a lower proportion of pathological AET (11.1% vs. 20.5%) and higher mean nocturnal baseline impedance (MNBI; 2472 vs. 1745 Ω) [1]. This pattern may reflect frequent reflux events not captured by acid exposure alone. However, TRE thresholds vary by region and recording system, and MNBI values also differ across populations [3, 4]. Moreover, the number of reflux episodes alone may not reliably predict proton pump inhibitor (PPI) response, whereas impedance metrics may inform treatment expectations [5]. Therefore, TRE and MNBI should be interpreted as adjunctive phenotype markers rather than stand-alone treatment triggers [3-5]. We suggest a provisional framework stratified by integrated reflux metrics. Patients with AET > 4% and regionally abnormal MNBI may represent an acid-predominant phenotype for whom acid suppression remains the cornerstone of therapy [6, 7]. Those with AET < 4% but elevated TRE or abnormal MNBI, whom the authors reclassify as inconclusive GERD, may represent a reflux event-predominant phenotype warranting focused evaluation of symptom-reflux association and expected treatment response [7, 8]. Non-acid-targeted strategies may include postprandial alginate, meal timing, and evaluation of behavioural regurgitation mechanisms [7]. When high GSS coexists with physiologic metrics across all reflux parameters, careful assessment for reflux hypersensitivity, functional heartburn, visceral hypersensitivity, and oesophageal hypervigilance is warranted, rather than reflexive GERD treatment escalation [4, 7]. The contribution by Chan et al. is timely and clinically relevant. As the field moves toward region-specific diagnostic criteria, we encourage equal emphasis on phenotype-guided management algorithms. Future consensus statements should consider separating regional diagnostic thresholds from treatment thresholds, ensuring that improved detection does not inadvertently lead to overtreatment in Asian populations. Jiahao Liu: investigation, methodology, writing – original draft. Yang Fu: supervision, visualization, writing – review and editing. The authors have nothing to report. This article is linked to Chan et al. papers. To view this article, visit https://doi.org/10.1111/apt.70713. Data sharing not applicable to this article as no datasets were generated or analysed during the current study.