Kelly HW, Sternberg AL, Lescher R, et al. Effect of Inhaled Glucocorticoids in Childhood on Adult Height. N Engl J Med 2012 Sep 6;367:904-912.
PMID: 22938716
http://www.nejm.org/doi/full/10.1056/NEJMoa1203229
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ORIGINAL ARTICLE
Effect of Inhaled Glucocorticoids in Childhood on Adult Height
H. William Kelly, Pharm.D., Alice L. Sternberg, Sc.M., Rachel Lescher, M.D., Anne L. Fuhlbrigge, M.D., Paul Williams, M.D., Robert S. Zeiger, M.D., Ph.D., Hengameh H. Raissy, Pharm.D., Mark L. Van Natta, M.H.S., James Tonascia, Ph.D., and Robert C. Strunk, M.D. for the CAMP Research Group
N Engl J Med 2012; 367:904-912 September 6, 2012
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 ?g 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.)
Supported by contracts with the National Heart, Lung, and Blood Institute (NO1-HR-16044, 16045, 16046, 16047, 16048, 16049, 16050, 16051, and 16052) and General Clinical Research Center grants from the National Center for Research Resources (M01RR00051, M01RR0099718-24, M01RR02719-14, and RR00036). Phases 2 and 3 of the CAMP Continuation Study were supported by grants from the National Heart, Lung, and Blood Institute (U01HL075232, U01HL075407, U01HL075408, U01HL075409, U01HL075415, U01HL075416, U01HL075417, U01HL075419, U01HL075420, and U01HL075408).
Dr. Kelly reports serving on steering committees for and receiving consulting fees from AstraZeneca, GlaxoSmithKline, Merck, and Novartis; Dr. Fuhlbrigge, receiving consulting fees from Merck, GlaxoSmithKline, Dmagi, Lovelace Respiratory Research Institute, and Sunovion and serving as a member of an adjudication committee for studies sponsored by AstraZeneca, GlaxoSmithKline, Merck, and Novartis; Dr. Williams, receiving lecture fees from GlaxoSmithKline; and Dr. Zeiger, serving on a steering committee for a study sponsored by GlaxoSmithKline and receiving consulting fees from Aerocrine, AstraZeneca, Genentech, GlaxoSmithKline, MedImmune, Novartis, Schering-Plough, and Sunovion and grant support from Aerocrine, Genentech, GlaxoSmithKline, MedImmune, Merck, and Thermofisher. No other potential conflict of interest relevant to this article was reported.
Disclosure forms provided by the authors are available with the full text of this article at NEJM.org.
This article was published on September 3, 2012, at NEJM.org.
SOURCE INFORMATION
From the University of New Mexico, Albuquerque (H.W.K., H.H.R.); Johns Hopkins University, Baltimore (A.L.S., M.L.V.N., J.T.); Washington University, St. Louis (R.L., R.C.S.); Alaska Native Medical Center, Anchorage (R.L.); Brigham and Women's Hospital, Boston (A.L.F.); University of Washington, Seattle (P.W.); and the University of California, San Diego, and Kaiser Permanente Southern California Region, San Diego (R.S.Z.).
Address reprint requests to Dr. Kelly at 9828 Guadalupe Trail NW, Albuquerque, NM 87114, or at hwkelly@salud.unm.edu.
Additional members of the Childhood Asthma Management Program (CAMP) Research Group are listed in the Supplementary Appendix, available at NEJM.org.