Gastro-oesophageal reflux treatment for prolonged non-specific cough in children and adults (Review)

Background
Gastroesophageal reflux disease (GORD) is said to be the causative factor in up to 41% of adults with chronic cough. However cough and GORD are common ailments and their co-existence by chance is high. Also cough can induce reflux episodes. Treatment for GORD includes conservative measures (diet manipulation), pharmaceutical therapy (motility or prokinetic agents, H2-antagonist and proton pump inhibitors (PPI)) and fundoplication.

Objectives
To evaluate the efficacy of GORD treatment on chronic cough in children and adults with GORD and prolonged cough that is not related to an underlying respiratory disease i.e. non-specific chronic cough.

Search strategy
We searched the Cochrane Register of Controlled Trials (CENTRAL), the Cochrane Airways Group Specialised Register, MEDLINE and EMBASE databases, review articles and reference lists of relevant articles. The date of last search was 24th April 2009.

Selection criteria
All randomised controlled trials (RCTs) on GORD treatment for cough in children and adults without primary lung disease.

Data collection and analysis
Two review authors independently assessed trial quality and extracted. Study authors were contacted for further information.

Main results
Eighteen studies (5 paediatric, 13 adults) were included. None of the paediatric studies could be included in meta-analysis. In adults, analysis on use of H2 antagonist, motility agents and conservative treatment for GORD were not possible (from lack of data) and there were no controlled studies on fundoplication as an intervention. Nine adult studies comparing PPI (two to three months) to placebo were analysed for various outcomes in themeta-analysis. Enrolment of participants subjects for two studies were primarily frommedical clinics and another eight studies were otolaryngology clinic patients or patients with laryngeal symptoms. Using “intention to treat”, pooled data from studies resulted in no significant difference between treatment and placebo in total resolution of cough, Odds Ratio 0.46 (95% confidence interval (CI) 0.19 to 1.15). Pooled data revealed no overall significant improvement in cough outcomes (end of trial or change in cough scores). Significant differences were only found in sensitivity analyses. A significant improvement in change of cough scores was found in end of intervention (two to three months) in those receiving PPI with a standardised mean difference of - 0.41 (95% CI -0.75 to -0.07) using generic inverse variance analysis on cross over trials. Two studies reported improvement in cough after five days to two weeks of treatment.

Authors’ conclusions
There is insufficient evidence to definitely conclude that GORD treatment with PPI is universally beneficial for cough associated with GORDin adults. The beneficial effect was only seen in sub-analysis. The optimal duration of such a trial of therapy to evaluate response could not be ascertained although two RCTs reported significant change by 2-weeks of therapy. Clinicians should be cognisant of a period (natural resolution with time) and placebo effect in studies that utilise cough as an outcome measure. Future paediatric and adult studies should be double blind, randomised controlled, parallel design, using treatments for at least two months, with validated subjective and objective cough outcomes and include ascertainment of time to respond as well as assessment of acid and/or non-acid reflux.