Anti-histamines for prolonged non-specific cough in children

BACKGROUND: Non-specific cough is defined as non-productive cough in the absence of identifiable respiratory disease or known aetiology. It is commonly seen in paediatric practice. These children are treated with a variety of therapies including anti-histamines. Also, anti-histamines are advocated as an empirical treatment in adults with chronic cough. OBJECTIVES: To evaluate the effectiveness of anti-histamines in treating children with prolonged non-specific cough. SEARCH STRATEGY: We searched the Cochrane Register of Controlled Trials (CENTRAL), MEDLINE, OLDMEDLINE and EMBASE databases. The latest searches were performed in November 2009. SELECTION CRITERIA: All randomised controlled trials comparing anti-histamines with a placebo or placebo-like medication with cough as an outcome, where cough is not primarily related to an underlying respiratory disorder such as cystic fibrosis, asthma, or suppurative lung disease. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed study quality and extracted data. MAIN RESULTS: Three included therapeutic studies had 182 randomised participants with 162 completing the trials although in one study, children with recurrent wheeze were also included. The four included safety evaluation studies randomised 3166 participants with 2862 completing the trials. Clinical heterogeneity was evident and limited data prevented combining data for meta-analysis. The two larger therapeutic studies described significant improvement in both the intervention and the placebo/placebo-like arms with no significant difference between the two groups. In the study with the smallest sample size, cetirizine (a second generation anti-histamine) was significantly more efficacious than placebo in reducing chronic cough in children associated with seasonal allergic rhinitis, and the effect was seen within two weeks of therapy. In contrast three of the larger evaluation studies that enrolled children with allergic rhinitis described a non-significant increase in cough as an adverse event. Combined data from the four safety evaluation studies revealed a non-significant difference between groups (OR 1.47 , 95% CI 0.86, 2.49) for cough as an adverse event but the trend favoured the placebo arm. AUTHORS' CONCLUSIONS: This review has significant limitations. However, our finding of uncertain efficacy of anti-histamines for chronic cough are similar to that for acute cough in children. In contrast to recommendations in adults with chronic cough, anti-histamines cannot be recommended as empirical therapy for children with chronic cough. If anti-histamines were to be trialled in these children, current data suggest a clinical response (time to response) occurs within two weeks of therapy. However the use of anti-histamines in children with non-specific cough has to be balanced against the well known risk of adverse events especially in very young children.