NIH-funded study finds potential small effect on growth rate should be balanced against proven health benefits
Adults who had been treated previously with the inhaled corticosteroid budesonide as part of a children’s clinical study were, on average, about half an inch shorter than their study counterparts who were not treated with inhaled corticosteroids, according to research funded by the National Institutes of Health. The half inch difference had been observed when the study participants were children, showing that, while the effect on height does not go away, it also does not get worse, the researchers say.
These findings come from a continued follow-up of 1,041 participants in the Childhood Asthma Management Program (CAMP) clinical trial, sponsored by the NIH’s National Heart, Lung, and Blood Institute (NHLBI). This is the first large prospective randomized study to follow children until they reached their final adult height since the association between inhaled corticosteroid use and decreased growth rate in children was first reported in the early 1990s.
The study will be published in the New England Journal of Medicine on Sept. 3, to coincide with a presentation at the European Respiratory Society Annual Congress in Vienna, Austria.
“The study provides an answer to a longstanding question about what happens long-term to children who experience effects on their growth rate when they begin inhaled corticosteroids therapy for asthma,” said Gary Gibbons, M.D., director of the NHLBI. “It clarifies that they do not eventually catch up as they age or fall further behind their peers.”
Gibbons added that while the persistence of this effect on height is a noteworthy finding, it must be considered in the larger context that many studies have proven the superior benefits of inhaled corticosteroids on improving asthma control and preventing exacerbations in children.
The researchers also found that the height effect was dependent on medication dosage, as higher daily doses of the inhaled corticosteroid per weight of the child were associated with lower adult height.
“This suggests that finding the minimum dose required to control each child’s asthma could help mitigate any potential effects on height,” noted lead study researcher William Kelly, Pharm.D., professor emeritus of pediatrics and pharmacy at the University of New Mexico Health Sciences Center, Albuquerque.
“This study demonstrates the value of follow-up studies to clinical trials,” said James Kiley, Ph.D., director of the NHLBI’s Division of Lung Diseases. “By understanding the long-term benefits and potential side effects of inhaled corticosteroids, we can help parents and physicians make informed choices for treatment.”
CAMP involved 1,041 children who were between 5 and 12 years old when they were enrolled in the study between 1993 and 1995. It compared the effects of daily therapies with the inhaled corticosteroid budesonide (400 micrograms per day), the non-steroidal inhaled therapy nedocromil, and a placebo on asthma control, lung development, and growth rate.
With four to six years of treatment, the nedocromil group had similar results as placebo, while children taking budesonide showed many improvements, such as fewer symptoms, fewer acute asthma attacks, fewer hospitalizations, and reduced airway hyperresponsiveness. The children in the budesonide group did experience a mild reduction in their growth rate during the first year of treatment that resulted in the group, on average, being about half an inch shorter than the children in the placebo and nedocromil groups. This effect persisted but did not increase over the duration of the clinical trial.
For this follow-up study, the researchers re-recruited the original CAMP participants and tracked their height, weight, and lung function every year for 12 more years, to an average participant age of 25. During that time, the participants were observed, but they were no longer treated for their asthma by study personnel; instead, they received asthma treatment from their personal physicians.
The researchers obtained adult height values for 943 of the original 1,041 CAMP participants, and observed a 0.47 inch difference in average height for those originally in the budesonide group, similar to the difference seen in the initial study. The deficit in growth rate was seen primarily in prepubertal children (girls 5-10 years of age and boys 5-11 years of age). These follow-up results confirmed that the effect on height during the initial treatment did not progress and was not cumulative, but it did persist to adulthood.
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The CAMP trial and CAMP Continuation Study were supported by NHLBI contracts NO1-HR-16044, 16045, 16046, 16047, 16048, 16049, 16050, 16051, and 16052. The CAMP Continuation Study/Phases 2 and 3 were supported by NHLBI grants U01HL075232, U01HL075407, U01HL075408, U01HL075409, U01HL075415, U01HL075416, U01HL075417, U01HL075419, U01HL075420, and U01HL075408.
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