COPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark.
COPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark.
J Allergy Clin Immunol. 2017 Aug;140(2):431-436. doi: 10.1016/j.jaci.2016.09.041. Epub 2016 Dec 21.
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.
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.
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.
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.
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.
评估吸入性皮质类固醇（ICSs）全身效应的药效学通常通过测量 24 小时尿游离皮质醇（UFC）排泄量来完成。评估短期小腿生长速度（LLGR）的测径术是一种使用较少的替代方法。
本研究的主要目的是比较 LLGR 和 24 小时 UFC 排泄量在评估哮喘青春期前儿童全身暴露于 ICSs 中的敏感性。次要目的是评估影响传统单腿非参数法和新双腿参数法计算的 LLGR 精度的因素。
该研究评估了 60 名年龄在 5 至 12 岁之间患有轻度哮喘的儿童，他们参加了一项 ICS 随机对照试验，并进行了 LLGR 和 24 小时 UFC 排泄量的纵向伴随评估。通过配对 t 检验，比较安慰剂导入期和 ICS 治疗期的 LLGR 和 24 小时 UFC 值，分析安全性评估的敏感性。通过方差分析和 Levene 检验分析可能影响 LLGR 的因素。
与安慰剂导入期相比，ICS 治疗期的平均 LLGR 显著降低：0.18mm/wk（SD，0.55mm/wk）与 0.45mm/wk（SD，0.39mm/wk），平均差异为 0.27mm/wk（95%CI，0.05-0.48mm/wk；P=0.02）。相反，24 小时 UFC 排泄量没有差异：6.91nmol/mmol（SD，4.67nmol/mmol）与 7.58nmol/mmol（SD，6.17nmol/mmol），平均差异为 0.67nmol/mmol（95%CI，-1.13 至 2.48nmol/mmol；P=0.46）。我们观察到，儿童年龄或性别、研究者或测量季节对参数确定的 LLGR 没有显著影响，但对非参数 LLGR 有一些影响。
这些发现表明，与 24 小时 UFC 排泄量相比，测径术是评估 ICSs 全身效应的更敏感的药效学指标，参数确定的 LLGR 可提高该方法的灵敏度。这些发现应在未来得到立法机构的考虑。
