Long-term use of inhaled budesonide is associated not only with slowed growth in prepubertal children, but with reduced final adult height as well.
An 8-year observational study found that children who had used budesonide during an asthma treatment trial were more than 1 cm shorter than those who used nedocromil or placebo. The findings suggest that glucocorticoid-related growth impairment has a lasting effect on potential adult height, H. William Kelly, Pharm.D., and his colleagues wrote in the Sept. 3 issue of the New England Journal of Medicine (2012;367:904-12 [doi: 10.1056/NEJMoa1203229]).
The prospective study followed 943 children who had participated in the Childhood Asthma Management Program (CAMP) trial. CAMP randomized children with asthma aged 5-13 years to placebo, 400 mcg/day budesonide, or 16 mg/day nedocromil.
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Children who used budesonide as an asthma treatment trial were found to be shorter than others.
Initial follow-up averaged 4.3 years, with height measured once or twice a year for the subsequent 8 years. Final height was measured at a mean age of 25 years.
The mean adult height in the budesonide group was 171.1 cm – significantly shorter than the 172.3 cm in the placebo group. Mean adult height in the nedocromil group was almost the same as in the placebo group (172.1 cm).
Women in the budesonide group were particularly affected; they were a mean of 1.8 cm shorter than women in the placebo group. Men who took budesonide were a mean of 0.8 cm shorter than men who took placebo as children.
During the first 2 years of the CAMP trial, growth had already slowed, showing a 1.3-cm difference between the budesonide and placebo groups. At the end of that trial, the difference was 1.2 cm, a deficit that did not change as the patients entered young adulthood.
Final height was related to daily dosage during the randomized trial, with a decrement of 0.1 cm for each microgram per kilogram of budesonide. Several baseline characteristics were also significantly related to lower adult height, including Hispanic ethnicity and being female, or having a higher Tanner stage, greater body mass index, longer duration of asthma, and low vitamin D levels.
Since the CAMP trial concluded, research has shown that 200 mcg/day budesonide in a dry-powder inhaler is sufficient to control mild to moderate asthma and prevent exacerbations in children. "Even at this lower dose, there was a reported mean reduction of 1.0 cm in height during the first 2 years of therapy," the investigators noted. "Although the systemic effects of inhaled glucocorticoids are dose dependent, they are also dependent on the therapeutic index of the specific inhaled glucocorticoid and the delivery device used. Thus, it seems prudent to select inhaled glucocorticoids and devices with higher therapeutic indexes, and to use them in the lowest effective doses in children with persistent asthma."
Ultimately, they concluded, parents and physicians must work together to decide the risk-benefit ratio that is most appropriate and acceptable for each individual patient.
"In the information about inhaled glucocorticoids and their side effects that is provided to parents, the potential effect on adult height must be balanced against the large and well-established benefits of these drugs in controlling persistent asthma," concluded Dr. Kelly of the University of New Mexico, Albuquerque, and his coauthors.
The CAMP trial and its observational study were funded by the National Heart, Lung, and Blood Institute and the National Center for Research Resources. Dr. Kelly serves on steering committees for and has received consulting fees from AstraZeneca, GlaxoSmithKline, and other companies. His coauthors also reported multiple financial relationships with pharmaceutical companies.