Cochrane Corner Inhaled corticosteroids in children with persistent asthma: is there a dose response impact on growth? - an overview of Cochrane reviews Aniela I. Pruteanu 1 , Bhupendrasinh F. Chauhan 2 , Linjie Zhang 3 , Silvio O.M. Prietsch 3 , Francine M. Ducharme 1,4, * 1 Department of Paediatrics, University of Montreal, Montreal, Canada 2 Clinical Research Unit on Childhood Asthma, Research Centre, CHU Sainte-Justine, Montreal, Canada 3 Faculty of Medicine, Federal University of Rio Grande, Rio Grande, Brazil 4 Research Centre, CHU Sainte-Justine, Montreal, Canada WHY DO WE NEED THIS REVIEW? Because of their efficacy, inhaled corticosteroids (ICS) are the preferred first-line treatment for children with persistent asthma of all ages [1]. Their potential for growth suppression in children remains a concern for parents and physicians. Consequently, international guidelines recommend the use of inhaled corticoste- roids at the minimally effective dose [1]. Yet, the impact of increasing or decreasing doses of ICS on children’s linear growth is poorly described. The aim of this Cochrane Review [2] was to assess whether increasing the dose of ICS is associated with a slower linear growth, weight gain and skeletal maturation in children with asthma. WHAT COMPARISONS DID WE MAKE IN THE REVIEW? We selected for inclusion parallel-group, randomised trials evaluating the impact of different doses of the same ICS, using the same device in both groups, for a minimum of three months in children aged one to 17 years with persistent asthma. The primary outcome was linear growth velocity, that is, the pattern of growth measured repeatedly over time and adjusted for relevant covariates. Secondary outcomes included change over time in growth velocity, height, weight, body mass index and skeletal maturation. Using the rigorous Cochrane methodology, we identified 22 eligible trials, yet only 10 of them measured growth or other measures of interest. The aggregated data provided 17 group comparisons (3394 children with mild or moderate asthma) because some trials compared three ICS doses. Trials used different ICS (beclomethasone, budesonide, ciclesonide, fluticasone or mometasone) as monotherapy or as combination therapy with a long-acting ß2-agonist and generally compared low (50 to 100 mg) with low-to-medium doses (200 mg) daily doses (converted to mg HFA-beclomethasone equivalent) over 12 to 52 weeks. Two authors independently assessed the studies and did the data extraction. Additional unpublished data and information was obtained through collaboration with the study authors and pharmaceutical groups from six trials. It was originally intended to undertake subgroup analyses on age, baseline severity of the airway obstruction, ICS dose and concomitant use of non-steroidal anti-asthmatic drugs. However, the similarity across trials or inadequate reporting prevented such analyses. WHAT DID WE FIND? Three industry-funded trials with high methodological quality (resulting in four dose comparisons) contributed data to the main outcome [3–5]. They pertained to 728 school-aged children measured by stadiometry, who had mild or moderate asthma and were treated with one of three ICS molecules (fluticasone, ciclesonide or mometasone) in whom a dose difference  150 mg was compared over 52 weeks. A very small (0.20 cm/y) but statistically significant group difference in linear growth was observed over 12 months, with a lower growth velocity in the higher ICS dose group (Figure 1). Because the three trials lasted one year, the long-term impact of different ICS doses on growth velocity could not be explored beyond this period. The Paediatric Respiratory Reviews 16 (2015) 51–52 * Corresponding author. Contents lists available at ScienceDirect Paediatric Respiratory Reviews http://dx.doi.org/10.1016/j.prrv.2014.10.002 1526-0542/ß 2014 Elsevier Ltd. All rights reserved.