GERD Treatment for Chronic Nonspecific Cough in Children and Adults

Background: Gastroesophageal reflux disease (GERD) is said to be the causative factor in up to 41 percent of adults with chronic cough. Treatment for GERD includes conservative measures (diet manipulation), pharmaceutical therapy (e.g., motility or prokinetic agents, histamine H-2 antagonists, proton pump inhibitors [PPIs]), and fundoplication. Objectives: To evaluate the effectiveness of GERD treatment on chronic cough in children and adults with GERD and prolonged cough that is not related to an underlying respiratory disease (i.e., nonspecific chronic cough). Search Strategy: The authors searched the Cochrane Airways Group Specialized Register, the Cochrane Register of Controlled Trials (CENTRAL), Medline, EMBASE, review articles, and reference lists of relevant articles. The date of last search was April 8, 2010. Selection Criteria: All randomized controlled trials (RCTs) on GERD treatment for cough in children and adults without primary lung disease. Data Collection and Analysis: Two review authors independently assessed trial quality and extracted data. They contacted study authors for further information. Main Results: The authors included 19 studies (six pediatric studies, 13 adult studies). None of the pediatric studies could be combined for meta-analysis. A single RCT in infants found that PPI use (compared with placebo) was not effective for cough outcomes (favoring placebo odds ratio [OR] = 1.61; 95% confidence interval [CI], 0.57 to 4.55), but those taking a PPI had significantly increased adverse events (OR = 5.56; 95% CI, 1.18 to 26.25; number needed to harm in four weeks = 11; 95% CI, 3 to 232). In adults, analysis of H2 antagonists, motility agents, and conservative treatment for GERD was not possible (lack of data), and there were no controlled studies of fundoplication. The authors analyzed nine adult studies comparing PPI (two to three months) with placebo for various outcomes in the meta-analysis. Using intention-to-treat, pooled data from studies resulted in no significant difference between treatment and placebo in total resolution of cough (OR = 0.46; 95% CI, 0.19 to 1.15). Pooled data revealed no overall significant improvement in cough outcomes (end of trial or change in cough scores). They only found significant differences in sensitivity analyses. The authors found a significant improvement in change of cough scores at the end of intervention (two to three months) in those receiving PPI (standardized mean difference = 0.41; 95% CI, 0.75 to 0.07) using generic inverse variance analysis on crossover trials. Two studies reported improvement in cough after five days to two weeks of treatment. Authors' Conclusions: PPI is not effective for cough associated with GERD symptoms in very young children (including infants) and should not be used for cough outcomes. There are insufficient data in older children to draw any valid conclusions. In adults, there is insufficient evidence to conclude definitely that GERD treatment with PPI is universally beneficial for cough associated with GERD. Clinicians should be cognizant of the period (natural resolution with time) and placebo effect in studies that utilize cough as an outcome measure. Future pediatric and adult studies should be double-blind, randomized controlled, and 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 nonacid reflux.