Effect of inhaled glucocorticoids in childhood on adult height

Abstract

Background: The use of inhaled glucocorticoids for persistent asthma causes a temporary reduction in growth velocity in prepubertal children. The resulting decrease in attained height 1 to 4 years after the initiation of inhaled glucocorticoids is thought not to decrease attained adult height.

Methods: We measured adult height in 943 of 1041 participants (90.6%) in the Childhood Asthma Management Program; adult height was determined at a mean (±SD) age of 24.9±2.7 years. Starting at the age of 5 to 13 years, the participants had been randomly assigned to receive 400 μg of budesonide, 16 mg of nedocromil, or placebo daily for 4 to 6 years. We calculated differences in adult height for each active treatment group, as compared with placebo, using multiple linear regression with adjustment for demographic characteristics, asthma features, and height at trial entry.

Results: Mean adult height was 1.2 cm lower (95% confidence interval [CI], -1.9 to -0.5) in the budesonide group than in the placebo group (P=0.001) and was 0.2 cm lower (95% CI, -0.9 to 0.5) in the nedocromil group than in the placebo group (P=0.61). A larger daily dose of inhaled glucocorticoid in the first 2 years was associated with a lower adult height (-0.1 cm for each microgram per kilogram of body weight) (P=0.007). The reduction in adult height in the budesonide group as compared with the placebo group was similar to that seen after 2 years of treatment (-1.3 cm; 95% CI, -1.7 to -0.9). During the first 2 years, decreased growth velocity in the budesonide group occurred primarily in prepubertal participants.

Conclusions: The initial decrease in attained height associated with the use of inhaled glucocorticoids in prepubertal children persisted as a reduction in adult height, although the decrease was not progressive or cumulative. (Funded by the National Heart, Lung, and Blood Institute and the National Center for Research Resources; CAMP ClinicalTrials.gov number, NCT00000575.).

Figure 1

Enrollment and Outcomes.

Figure 2. Effect of Budesonide on Adult Height

Panel A shows Tukey’s box plots of unadjusted height distribution at trial entry (at the age of 5 to 13 years), at 2 years, at the end of the trial, and at the time of adult-height determination for up to 311 participants receiving budesonide and 418 receiving placebo, according to sex. The bottom and top of each box are the 25th and 75th percentiles of the height distribution, respectively, and the horizontal line within the box is the median. The I bars indicate the range of the distribution that is not extreme (i.e., within 1.5 interquartile ranges of the 25th and 75th percentiles of the distribution), and the open circles show the extreme values in the height distribution. Panel B shows the adjusted mean difference in height between the budesonide group and the placebo group during follow-up. The I bars indicate 95% confidence intervals. Means have been adjusted for age, race or ethnic group, sex, clinic, asthma severity, asthma duration, and presence or absence of skin-test reactivity at trial entry. Mean values for times after time 0 (trial entry) have also been adjusted for height at trial entry.