Growth of Preschool Children at High Risk for Asthma Two Years after Discontinuation of Fluticasone

Background—The effect on linear growth of daily long-term inhaled corticosteroid (ICS) therapy in preschool-aged children with recurrent wheezing is controversial. Objective—To determine the effect of daily ICS given for 2 years on linear growth in preschool children with recurrent wheezing. Methods—Children ages 2 and 3 years with recurrent wheezing and positive modified asthma predictive indices were randomized to a two-year treatment period of fluticasone propionate CFC (176 mcg/day) or masked-placebo delivered by valved chamber with mask and then followed 2 © 2011 American Academy of Allergy, Asthma and Immunology. Published by Mosby, Inc. All rights reserved. aCorresponding author for proof and reprints: Theresa Guilbert, M.D., The Department of Pediatrics, University of WisconsinMadison, 600 Highland Avenue, K4/944, CSC-4108, Madison, WI 53716, Phone: 608-265-7959, Fax: 608-265-0510, tguilbert@wisc.edu. Clinical Implications: The potential for reduced linear growth among children on inhaled corticosteroids who are two years of age and <17 kg should be balanced with level of asthma control to maximize the benefit-risk ratio of treatment. Clinical Trials Registry: ClinicalTrials.gov number, NCT00272441. This study was part of a large, multi-center clinical trial conducted through the NHLBI-sponsored Childhood Asthma Research and Education (CARE) Network. NHLBI funded this study. The role of commercial sponsors was limited to donating drug and matched placebo that they did after reviewing the drafted protocol. The text of the manuscript was made available to all the commercial sponsors 2 weeks prior to finalization for comments. All the authors had full access to all of the data in this study and take complete responsibility for the integrity of the data and the accuracy of the data analysis. All authors have seen and approved the submission of this version of the manuscript and take full responsbility for the manuscript. The declaration of all sources of funding for each author are listed below. Potential conflicts of interest are also detailed on the COI forms which will be faxed to the JACI office at the time of manuscript submission. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access Author Manuscript J Allergy Clin Immunol. Author manuscript; available in PMC 2012 November 1. Published in final edited form as: J Allergy Clin Immunol. 2011 November ; 128(5): 956–963.e7. doi:10.1016/j.jaci. 2011.06. 027. N IH PA Athor M anscript N IH PA Athor M anscript N IH PA Athor M anscript years off study medication. Height growth determined by stadiometry was compared between treatment groups. Results—In the study cohort as a whole, the fluticasone group did not have significantly less linear growth than the placebo-group [change in height from baseline difference (ΔHt) of −0.2 cm (95% CI, −1.1, 0.6)] two years after discontinuation of study treatment. In post-hoc analyses, children 2 years old and who weighed < 15 kg at enrollment treated with fluticasone had less linear growth compared to placebo [ΔHt of −1.6 cm (95% CI, −2.8, −0.4), p=0.009]. Conclusion—Linear growth was not significantly different in high-risk, recurrent wheezing preschool age children treated with CFC fluticasone 176 mcg/day compared to placebo 2 years after fluticasone is discontinued. However, post-hoc subgroup analyses revealed that children who are younger in age and of lesser weight relative to the entire study cohort had significantly less linear growth, possibly due to a higher relative fluticasone exposure.