Shine Brian
Department of Clinical Biochemistry, John Radcliffe Hospital, Oxford, UK.
Ann Clin Biochem. 2008 Sep;45(Pt 5):467-75. doi: 10.1258/acb.2008.008028.
Reference intervals are used to distinguish between healthy and diseased state. Ideally, they are defined using specimens only from 'healthy' individuals, but this is often difficult or impossible. In order to use routine clinical laboratory data, outliers must be removed before the underlying distribution and changes related to age and sex can be modelled. This paper illustrates the process for plasma alkaline phosphatase (ALP). ALP levels are high in infancy and childhood, peak in adolescence, are stable from the early 20s and rise after the fourth decade. Three types of normalizing transformations (Logarithmic, Box-Cox and Cole's LMS) are compared.
Single ALP results from 75,328 individuals aged 0-80 years were binned by sex and age. The normalizing transformations were applied to each bin, outliers were removed and the normalizing transformations were reapplied to the remaining data. The normality of the transformed data was assessed by normal score plots and the Kolmogorov-Smirnov test. Fractional polynomials were used to model the underlying parameters of the transformations and the derived parametric reference intervals (mean +/- 1.96 standard deviations), separately for each sex as a whole and partitioned into two or three age ranges, with overlapping to give smooth transitions.
All transformations yielded acceptably normal data, but the LMS method gave the closest approximation to normal. Outlier rates were similar for each method. The derived reference ranges were similar for all the three methods. Splitting the data-set into several segments resulted in a better fit with the peak seen in adolescence.
Routine clinical laboratory specimens can be used to derive reference intervals.
参考区间用于区分健康状态和疾病状态。理想情况下，它们仅使用来自“健康”个体的样本进行定义，但这通常很难做到或根本无法实现。为了使用常规临床实验室数据，必须先去除异常值，然后才能对基础分布以及与年龄和性别相关的变化进行建模。本文阐述了血浆碱性磷酸酶（ALP）的分析过程。ALP水平在婴儿期和儿童期较高，在青春期达到峰值，从20岁出头开始稳定，并在40岁以后上升。比较了三种类型的标准化转换（对数转换、Box-Cox转换和Cole的LMS转换）。
将75328名年龄在0至80岁之间个体的单次ALP检测结果按性别和年龄进行分组。对每个组应用标准化转换，去除异常值，然后对剩余数据重新应用标准化转换。通过正态得分图和Kolmogorov-Smirnov检验评估转换后数据的正态性。使用分数多项式分别对每种性别的整体以及划分为两个或三个年龄范围（有重叠以实现平滑过渡）的转换基础参数和导出的参数参考区间（均值±1.96标准差）进行建模。
所有转换均产生了可接受的正态数据，但LMS方法给出的结果最接近正态分布。每种方法的异常值率相似。三种方法得出的参考范围相似。将数据集分成几个部分能更好地拟合青春期出现的峰值。
常规临床实验室样本可用于推导参考区间。
