Cortisol suppression as a surrogate marker for inhaled corticosteroid-induced growth retardation in children.
Exposure of inhaled corticosteroids (ICSs) in pediatrics results in adrenal suppression and growth inhibition. The objective of this study was to assess the relationship of ICS mediated growth retardation with cortisol suppression in asthmatic children. A meta-analysis approach was performed with 33 published articles. Growth velocity (GV) data were obtained from the literature for evaluation of growth. Cumulative cortisol suppression within 24h (CCS%) was calculated at steady state with a validated algorithm. Consolidated GV and CCS% data were employed for model development. A linear mixed effects model was developed to adequately describe the relationship between GV and CCS%. No impact of tested covariates was observed. Population estimate of the rate of change in GV was -0.06cm/year/CCS% (12.7%, coefficient of variation) for both stadiometry and knemometry methods. However, GV from stadiometry is expected to be approximately three fold higher than that from knemometry when cortisol suppression was not presented. The final model was evaluated with posterior predictive check and pattern check approaches. The results from this study elucidate CCS% as an excellent predictor of ICS mediated growth retardation in asthmatic children.
Xu
Jian
J
Department of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville, FL 32610, USA.
Sabarinath
Sreedharan Nair
SN
Derendorf
Hartmut
H
D000280:Administration, Inhalation; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage / Q000009:adverse effects*; D000465:Algorithms; D000818:Animals; D001249:Asthma / Q000150:complications; D015415:Biomarkers; D002648:Child; D003627:Data Interpretation, Statistical; D006130:Growth Disorders / Q000139:chemically induced*; D006801:Humans; D006854:Hydrocortisone / Q000037:antagonists & inhibitors*; D066298:In Vitro Techniques; D015233:Models, Statistical
D000305:Adrenal Cortex Hormones; D015415:Biomarkers; D006854:Hydrocortisone