Articulo Cientifico Sistema Digestivo

Cite this article as: BMJ, doi:10.1136/bmj.38677.559005.55 (published 5 December 2005)

Research

Systematic review and meta-analysis of randomised controlled trials of gastro-oesophageal reflux interventions for chronic cough associated with gastro-oesophageal reflux
A B Chang, T J Lasserson, T O Kiljander, F L Connor, J T Gaffney, L A Garske

Abstract
Objective To evaluate the efficacyof 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% confidenceinterval 0.04 to 1.27); number needed to treat (NNT) was 5 (harm 50 to ∞ 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 analysisshowed 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.

acid causes 21-41% of chronic non-specific cough.1 Guidelines onchronic cough suggest use of empirical treatment for GOR,4 5 including a therapeutic trial of three to six months of treatment for GORD.6 Although laboratory studies have shown a temporal relation between acid in the oesophagus and cough, some studies have shown that the cough resolves only after a mean of 169179 days after treatment.6 Other studies have shown that acid GORD is associated with, but isnot the cause of, cough.7 Current treatments for GORD include conservative measures (diet, positioning, etc), pharmaceuticals (acid suppressants such as histamine H2 receptor antagonists, and proton pump inhibitors; prokinetic agents such as domperidone, metoclopramide, and cisapride), and surgical approaches (fundoplication). These well established treatments for GOR, however, may not bebeneficial for associated cough or may increase respiratory morbidity.8 We examined the efficacy of treatments for GOR on nonspecific chronic cough in adults and children in a systematic review. This review is based on a Cochrane systematic review.9

Methods
We used QUOROM guidelines, Cochrane collaboration method, and software (RevMan 4.2) (see bmj.com). Studies in adults and children were eligibleif they were randomised controlled trials of any GORD treatment for chronic cough (lasting more than three weeks) where cough was an outcome and not primarily related to an underlying respiratory disorder. We classified the evaluated treatment regimens by type: anti-reflux conservative measures (for example, positioning, diet), H2 receptor antagonists, proton pump inhibitor, and surgical therapy.Our primary outcome was proportion of participants who were not cured at follow-up (failure to cure). Secondary outcomes were proportion of participants not substantially improved at follow-up, mean difference in cough indices (frequency of cough, scores, sensitivity), proportion who experienced adverse effects (such as rash, surgical morbidity, etc), and proportions who experienced complications...