Longitudinal growth in infants and young children treated with budesonide inhalation suspension for persistent asthma

Background: Results of recent growth studies suggest that inhaled glucocort icosteroids may affect growth in children. Objective: Three 52-week, open-label extension studies (studies A, B, and C ) were conducted to compare the effects of budesonide inhalation suspension (BIS) with conventional asthma therapy (CAT) on long-term safety, includin g intermediate-term growth, in 3 different pediatric asthma populations. Methods: Pediatric asthma patients (ages 6 months to 8 years) from 3 multic enter, randomized, 12-week, double-blind, placebo-controlled studies were e ligible to enroll in the 52-week, open-label extension studies. The extensi on studies were multicenter, randomized, open-label, active-controlled, par allel-group studies performed at 26 centers in the United States. Subjects in each extension study were randomized in a 2:1 ratio to receive either BI S or CAT. BIS was initially administered at a dose of 9.5 mg once (studies A and C) or twice daily (study B), with attempts made at each clinical visi t to gradually reduce the dose to the minimum effective dose that maintains asthma control, as judged by the investigator. CAT consisted of any availa ble therapy for asthma, including inhaled glucocorticosteroids in studies B and C only. Height SD scores, growth velocity, and skeletal age (only in s tudies B and C) were examined. Results: In total, 670 subjects were randomized; 223 subjects received CAT and 447 received BIS. Mean ages at entry were 63.0 months and 60.9 months i n CAT and BIS groups, respectively. Median total daily doses of BIS ranged from 0.5 to 1.0 mg and the mean duration of treatment exposure was 304 +/- 119 days and 342 +/- 83 days in CAT and BIS groups, respectively. Changes i n height SD scores differed significantly between the BIS and CAT groups in study A (-0.19, P =.003), and there was a small, statistically significant decrease in growth velocity (-0.8 cm/y, P =.002) in the BIS-treated group compared with the CAT group. No significant differences were observed betwe en BIS and CAT groups in the changes in height SD scores or in growth veloc ities in studies B (+0.10 and +0.7 cm/y, respectively) and C (+0.12 and +0. 8 cm/y, respectively). No differences in skeletal age were observed between BIS and CAT groups in studies B and C. Conclusion: There was a small, statistically significant decrease in growth velocity in the BIS-treated group compared with the CAT group in the study (study A) where inhaled glucocorticosteroid use was prohibited before entr y and in the CAT group during the study. In the studies (B and C) where inh aled glucocorticosteroids were allowed in the CAT group, no differences wer e observed in height SD scores or growth velocity. The clinical relevance o f these effects, including impact on final adult height, remain to be deter mined in prospectively planned studies that assess growth in children.