Prevalence of pathological acid exposure and reflux–cough temporal associations in adults with chronic cough: a systematic review and meta-analysis

Abstract

The contribution of gastro-oesophageal reflux to chronic cough remains uncertain because pathological acid exposure and temporal reflux–cough association represent distinct physiological abnormalities. The objective of this systematic review and meta-analysis was to estimate the prevalence of these two physiological phenotypes in adults undergoing multichannel intraluminal impedance–pH (MII-pH) monitoring and to explore potential sources of heterogeneity. PubMed, Scopus, Web of Science, and Google Scholar were searched from inception to July 2026. Observational studies of adults with chronic cough assessed by ambulatory MII-pH were eligible. Random-effects models with restricted maximum likelihood estimation pooled participant-level prevalence estimates. Heterogeneity was assessed using I², and leave-one-out and exploratory subgroup analyses were performed. 14 studies with 1,324 analysed patients were included. Five studies including 478 participants reported positive reflux-to-cough temporal associations, with a pooled prevalence of 35.30% (95% CI, 27.04%–43.57%; I²=67.98%). Five studies including 608 participants reported pathological distal acid exposure, with a pooled prevalence of 31.41% (95% CI, 16.76%–46.06%; I²=93.91%). Prevalence of acid-specific symptom association probability (SAP) positivity was 20.60% (95% CI, 10.88%–30.32%; I²=80.81%), while for weakly acidic/nonacid-specific SAP positivity – 24.09% (95% CI, 15.11%–33.06%; I²=72.85%). The need to have at least four cough events was associated with lower temporal-association prevalence; other subgroups showed no differences. Across selected adults undergoing MII-pH, positive reflux-to-cough temporal associations and pathological acid exposure were reported in substantial but highly variable proportions across studies. These estimates should not be interpreted as the proportion of chronic cough caused by reflux in the general population. High heterogeneity and evidence of non-acidic and bidirectional mechanisms speak in favour of standardization of monitoring and careful interpretation of physiological test positivity.