Abstract
BACKGROUND Asthma exacerbations occur frequently despite the regular use of asthma-controller therapies, such as inhaled glucocorticoids. Clinicians commonly increase the doses of inhaled glucocorticoids at early signs of loss of asthma control. However, data on the safety and efficacy of this strategy in children are limited. METHODS We studied 254 children, 5 to 11 years of age, who had mild-to-moderate persistent asthma and had had at least one asthma exacerbation treated with systemic glucocorticoids in the previous year. Children were treated for 48 weeks with maintenance low-dose inhaled glucocorticoids (fluticasone propionate at a dose of 44 μg per inhalation, two inhalations twice daily) and were randomly assigned to either continue the same dose (low-dose group) or use a quintupled dose (highdose group; fluticasone at a dose of 220 μg per inhalation, two inhalations twice daily) for 7 days at the early signs of loss of asthma control ("yellow zone"). Treatment was provided in a double-blind fashion. The primary outcome was the rate of severe asthma exacerbations treated with systemic glucocorticoids. RESULTS The rate of severe asthma exacerbations treated with systemic glucocorticoids did not differ significantly between groups (0.48 exacerbations per year in the highdose group and 0.37 exacerbations per year in the low-dose group; relative rate, 1.3; 95% confidence interval, 0.8 to 2.1; P = 0.30). The time to the first exacerbation, the rate of treatment failure, symptom scores, and albuterol use during yellowzone episodes did not differ significantly between groups. The total glucocorticoid exposure was 16% higher in the high-dose group than in the low-dose group. The difference in linear growth between the high-dose group and the low-dose group was -0.23 cm per year (P = 0.06). CONCLUSIONS In children with mild-to-moderate persistent asthma treated with daily inhaled glucocorticoids, quintupling the dose at the early signs of loss of asthma control did not reduce the rate of severe asthma exacerbations or improve other asthma outcomes and may be associated with diminished linear growth. (Funded by the National Heart, Lung, and Blood Institute; STICS ClinicalTrials.gov number, NCT02066129.)
| Original language | English (US) |
|---|---|
| Pages (from-to) | 891-901 |
| Number of pages | 11 |
| Journal | New England Journal of Medicine |
| Volume | 378 |
| Issue number | 10 |
| DOIs | |
| State | Published - Mar 8 2018 |
Funding
Supported by the National Heart, Lung, and Blood Institute. Dr. Jackson reports receiving fees for serving on an advisory board from Vectura Group, Boehringer Ingelheim, and GlaxoSmithKline and consulting fees from Novartis; Dr. Bacharier, receiving consulting fees and lecture fees from Aerocrine, GlaxoSmithKline, Genentech-Novartis, Teva Pharmaceuticals, and Boehringer Ingelheim, fees for serving on an advisory board and lecture fees from Merck, consulting fees from Cephalon, fees for serving on a data and safety monitoring board from DBV Technologies, lecture fees from AstraZeneca, honoraria for continuing medical education (CME) program development from WebMD-Medscape, and fees for serving on an advisory board from Sanofi, Vectura Group, and Circassia; Dr. Mauger, receiving drugs for trials from Merck and Boehringer Ingelheim; Dr. Chmiel, receiving honoraria from Nivalis Therapeutics, honoraria paid to his institution from Corbus Pharmaceuticals, and consulting fees from Verona Pharma, Catabasis, Albumedix, and Patara Pharma; Dr. Morgan, receiving fees for serving as co-chair of an epidemiologic study of cystic fibrosis for Genentech; Dr. Peters, receiving fees for serving on an advisory board from AstraZeneca, Boehringer Ingelheim, Sunovion Pharmaceuticals, Teva Pharmaceuticals, and Regeneron Pharmaceuticals- Sanofi, fees for serving on a data and safety monitoring board from Gilead Sciences, Genentech, and Novartis, fees for clinicaltrial adjudication from Quintiles, fees for CME WebEx from PRIME, and fees for a CME program from Haymarket Media Group; Dr. Cabana, receiving fees for serving on a speakers bureau from Merck and consulting fees from Thermo Fisher Scientific, Genentech, and Novartis; Dr. Martinez, receiving grant support from Johnson & Johnson and consulting fees from Compañía Agropecuaria Copeval and Commense; Dr. Pongracic, receiving study drugs from Boehringer Ingelheim, GlaxoSmithKline, Teva Pharmaceuticals, and Merck; Dr. Covar, receiving grant support from Roche and AstraZeneca; Dr. Gentile, receiving grant support and lecture fees from Stallergenes Greer; Dr. Israel, receiving consulting fees from AstraZeneca, Philips Respironics, Regeneron Pharmaceuticals, Bird Rock Bio, Nuvelution Pharmaceuticals, Vitaeris, and Entrinsic Health Solutions, receiving consulting fees and fees for serving on data and safety monitoring board from Novartis, serving as unpaid member of a data and safety monitoring board for a trial funded by Novartis, receiving travel support from Research in Real Life, receiving consulting fees, travel support, and study drugs from Teva Specialty Pharmaceuticals, receiving grant support from Genentech, receiving grant support and study drugs from Boehringer Ingelheim, receiving consulting fees and study drugs from GlaxoSmithKline and Merck, receiving study drugs from Sunovion, and receiving grant support and consulting fees from Sanofi; Dr. Ly, receiving lecture fees from ABcomm and fees for serving on an advisory board from Gilead Sciences; and Dr. Ross, receiving study drugs from Boehringer Ingelheim, Glaxo- SmithKline, and Merck and grant support and study drugs from Teva Pharmaceuticals. No other potential conflict of interest relevant to this article was reported.
ASJC Scopus subject areas
- General Medicine