Systematic review and meta-analysis of randomised controlled trials of gastro-oesophageal reflux interventions for chronic cough associated with gastro-oesophageal reflux

Abstract

Objective: To evaluate the efficacy of treatment for gastro-oesophageal reflux disease (GORD) on chronic cough in children and adults without an underlying respiratory disease.

Design: Systematic review and meta-analysis.

Data sources: Cochrane, Medline, and Embase databases, references from review articles.

Included studies: Randomised controlled trials on GORD treatment for cough in children and adults without primary lung disease. Two reviewers independently selected studies and extracted paediatric and adult data on primary (clinical failure) and secondary outcomes.

Results: 11 studies were included. Meta-analysis was limited to five studies in adults that compared proton pump inhibitors with placebo. All outcomes favoured proton pump inhibitors: the odds ratio for clinical failure (primary outcome) was 0.24 (95% confidence interval 0.04 to 1.27); number needed to treat (NNT) was 5 (harm 50 to infinity to benefit 2.5). For secondary outcomes, the standardised mean difference between proton pump inhibitors and placebo was -0.51 (-1.02 to 0.01) for mean cough score at the end of the trial and -0.29 (-0.62 to 0.04) for change in cough score at the end of the trial. Subgroup analysis with generic inverse variance analysis showed a significant mean change in cough (-0.41 SD units, -0.75 to -0.07).

Conclusion: Use of a proton pump inhibitor to treat cough associated with GORD has some effect in some adults. The effect, however, is less universal than suggested in consensus guidelines on chronic cough and its magnitude of effect is uncertain.

Fig 1

Details of included and excluded trials

Fig 2

Meta-analysis of primary outcome (clinical failures—that is, patients still had cough at the end of the trial or reporting period), analyses by intention to treat (49 participants included in meta-analysis)

Fig 3

Meta-analysis of standardised cough scores at end of intervention (77 participants included in meta-analysis)

Fig 4

Meta-analysis of data from the two crossover trials assessing mean change in symptoms (subanalysis). Using generic inverse variance for crossover studies, use of proton pump inhibitors was significantly more likely than placebo to reduce cough scores at end of intervention, -0.41 SD units (-0.75 to -0.07)