Randomized Trial of Once-Daily Fluticasone Furoate in Children with Inadequately Controlled Asthma.

OBJECTIVE: To evaluate the dose-response, efficacy, and safety of fluticasone furoate (FF; 25 µg, 50 µg, and 100 µg), administered once daily in the evening during a 12-week treatment period to children with inadequately controlled asthma. STUDY DESIGN: This was a Phase IIb, multicenter, stratified, randomized, double-blind, double-dummy, parallel-group, placebo- and active-controlled study in children aged 5-11 years with inadequately controlled asthma. The study comprised a 4-week run-in period, 12-week treatment period, and 1-week follow-up period. Children were randomized to receive either placebo once daily, fluticasone propionate (FP) 100 µg twice daily, FF 25 µg, FF 50 µg, or FF 100 µg each once daily in the evening. Primary endpoint was the mean change from baseline in daily morning peak expiratory flow (PEF) averaged over weeks 1-12. Adverse events (AEs) also were investigated. RESULTS: In total, 593 children were included in the intent-to-treat population. The difference vs placebo in change from baseline daily morning PEF averaged over weeks 1-12 was statistically significant for the FF 25, FF 50, FF 100, and FP 100 groups (18.6 L/min, 19.5 L/min, 12.5 L/min, and 14.0 L/min, respectively; P < .001 for all). The incidence of AEs was greater in the FF groups (32%-36%) than in the placebo group (29%); the most frequent AE was cough. CONCLUSION: FF and FP resulted in significant improvements in morning PEF compared with placebo, suggesting that they are effective treatments for children with inadequately controlled asthma. All treatments were well tolerated; no new safety concerns were identified. TRIAL REGISTRATION: ClinicalTrials.gov:NCT01563029.

Genome-wide association study of the age of onset of childhood asthma.

BACKGROUND: Childhood asthma is a complex disease with known heritability and phenotypic diversity. Although an earlier onset has been associated with more severe disease, there has been no genome-wide association study of the age of onset of asthma in children. OBJECTIVE: We sought to identify genetic variants associated with earlier onset of childhood asthma. METHODS: We conducted the first genome-wide association study of the age of onset of childhood asthma among participants in the Childhood Asthma Management Program (CAMP) and used 3 independent cohorts from North America, Costa Rica, and Sweden for replication. RESULTS: Two single nucleotide polymorphisms (SNPs) were associated with earlier onset of asthma in the combined analysis of CAMP and the replication cohorts: rs9815663 (Fisher P= 2.31 × 10(-8)) and rs7927044 (P= 6.54 × 10(-9)). Of these 2 SNPs, rs9815663 was also significantly associated with earlier asthma onset in an analysis including only the replication cohorts. Ten SNPs in linkage disequilibrium with rs9815663 were also associated with earlier asthma onset (2.24 × 10(-7)

Variability in asthma severity in pediatric subjects with asthma previously receiving short-acting beta2-agonists.

OBJECTIVE: An analysis of 5 double-blinded, randomized, 12-week asthma trials was undertaken to evaluate pediatric subjects (4 to 11 years; n=276) who were previously receiving short-acting beta2-agonists alone and subsequently received treatment with placebo. At baseline, all subjects met National Asthma Education and Prevention Program criteria for moderate/severe asthma. STUDY DESIGN: Asthma severity was categorized individually for symptoms, albuterol use, and morning peak expiratory flow and then overall taking into account all three parameters. RESULTS: Subjects spent the majority of weeks (55%) in the moderate/severe category. Subjects spent approximately 48%, 31%, and 22% of weeks in intermittent, mild, and moderate/severe categories and 57%, 27%, and 15% of weeks, respectively, based on asthma symptoms and albuterol use. Subjects spent approximately 62%, 31%, and 8% of weeks in intermittent/mild, moderate, and severe categories, based on peak expiratory flow; however, >35% of subjects exhibited >or=15 changes in asthma severity classification, based on peak expiratory flow. CONCLUSIONS: Asthma is a disease with varying symptomatology, and pediatric subjects frequently move between severity categories, especially in children with inadequate asthma control. These data also emphasize that asthma severity cannot be determined in many pediatric subjects by discrete, point-in-time assessments of lung function, albuterol use, or asthma symptoms. Failure to recognize this problem may contribute to underestimation of disease severity in pediatric subjects.