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Background Pharmacodynamic assessment of the systemic effect of inhaled corticosteroids (ICSs) is often done by measuring 24-hour urine free cortisol (UFC) excretion. Knemometry assessing short-term lower-leg growth rate (LLGR) is a more rarely used alternative. Objective The primary aim of this study was to compare the sensitivity of LLGR and 24-hour UFC excretion for evaluating systemic exposure to ICSs in prepubertal children with asthma. The secondary aim was to evaluate factors influencing the precision of LLGR calculated by the traditional 1 leg nonparametric method versus a new 2 leg parametric method. Methods The study evaluated 60 children with mild asthma aged 5 to 12 years participating in a randomized controlled trial of ICSs with longitudinal concomitant assessments of LLGR and 24-hour UFC excretion. The sensitivity of the safety assessments was analyzed by comparing LLGR and 24-hour UFC in the placebo run-in period with values in the ICS treatment period by using paired t tests. Factors with a potential influence on LLGR were analyzed by means of ANOVA and the Levene test of homogeneity. Results The mean LLGR was significantly reduced during the ICS versus placebo run-in periods: 0.18 mm/wk (SD, 0.55 mm/wk) versus 0.45 mm/wk (SD, 0.39 mm/wk), with a mean difference of 0.27 mm/wk (95% CI, 0.05-0.48 mm/wk; P = .02). In contrast, there was no difference in 24-hour UFC excretion: 6.91 nmol/mmol (SD, 4.67 nmol/mmol) versus 7.58 nmol/mmol (SD, 6.17 nmol/mmol), with a mean difference of 0.67 nmol/mmol (95% CI, −1.13 to 2.48 nmol/mmol; P = .46). We observed no significant difference in parametric determined LLGR caused by the child's age or sex, investigator, or season of measurement, whereas some differences were observed for the nonparametric LLGR. Conclusion These findings suggest that knemometry is a more sensitive pharmacodynamic measure of systemic effects of ICSs than 24-hour UFC excretion and that a parametric determination of LLGR increases the sensitivity of the method. These findings should be considered by legislative authorities in the future. [ABSTRACT FROM AUTHOR]

Background: Measurement of short-term lower-leg growth rate in children by means of knemometry has become established as an integral part of the available measures of systemic activity of topical steroids in children. Objective: We sought to determine the effects of clinically effective doses of the novel inhaled corticosteroid ciclesonide on lower-leg growth rate and hypothalamic-pituitary-adrenal axis function in children with asthma. Methods: In a double-blind, placebo-controlled, 4-period crossover study, 24 children aged 6 to 12 years sequentially received ciclesonide (40, 80, and 160 μg) in randomized order once daily in the evening. Each 2-week treatment period was followed by a 2-week washout period. Knemometry was performed at the beginning and end of each treatment period. Cortisol levels in 12-hour overnight urine were measured at the end of each treatment period. Results: No statistically significant differences were seen in lower-leg growth rates between any of the ciclesonide treatments and placebo. Lower-leg growth rates were 0.412 mm/wk for placebo, 0.425 mm/wk for 40 μg of ciclesonide, 0.397 mm/wk for 80 μg of ciclesonide, and 0.370 mm/wk for 160 μg of ciclesonide. There was no statistically significant dose-response effect. Likewise, no statistically significant differences or dose-response effects were found for urinary cortisol adjusted for creatinine. Conclusion: Short-term lower-leg growth rate and hypothalamic-pituitary-adrenal axis function are not affected by treatment with ciclesonide in doses intended for clinical use in children. [Copyright &y& Elsevier]

Scarce data on systemic activity of corticosteroid eye drops are available in children. Two weeks treatment with fluorometholone eye drops in a case series of five children caused growth suppression detected by knemometry. The suppression had no impact on height growth during the following year. [ABSTRACT FROM AUTHOR]

Scarce data on systemic activity of corticosteroid eye drops are available in children. Two weeks treatment with fl uorometholone eye drops in a case series of fi ve children caused growth suppression detected by knemometry. The suppression had no impact on height growth during the following year. [ABSTRACT FROM AUTHOR]