Age- and size-related reference ranges: a case study of spirometry through childhood and adulthood

Age-related reference ranges are useful for assessing growth in children. The LMS method is a popular technique for constructing growth charts that model the age-changing distribution of the measurement in terms of the median, coefficient of variation and skewness. Here the methodology is extended to references that depend on body size as well as age, by exploiting the flexibility of the generalised additive models for location, scale and shape (GAMLSS) technique. GAMLSS offers general linear predictors for each moment parameter and a choice of error distributions, which can handle kurtosis as well as skewness. A key question with such references is the nature of the age-size adjustment, additive or multiplicative, which is explored by comparing the identity link and log link for the median predictor.There are several measurements whose reference ranges depend on both body size and age. As an example, models are developed here for the first four moments of the lung function variables forced expiratory volume in 1 s (FEV(1)), forced vital capacity (FVC) and FEV(1)/FVC in terms of height and age, in a data set of 3598 children and adults aged 4 to 80 years. The results show a strong multiplicative association between spirometry, height and age, with a large and nonlinear age effect across the age range. Variability also depends nonlinearly on age and to a lesser extent on height. FEV(1) and FVC are close to normally distributed, while FEV(1)/FVC is appreciably skew to the left. GAMLSS is a powerful technique for the construction of such references, which should be useful in clinical medicine.