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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 (FEV1), forced vital capacity (FVC) and FEV1/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. FEV1 and FVC are close to normally distributed, while FEV1/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. Copyright © 2008 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

We regret that the following acknowledgement was omitted in error from our paper 'Age- and size-related reference ranges: A case study of spirometry through childhood and adulthood', by T. J. Cole, S. Stanojevic, J. Stocks, A. L. Coates, J. L. Hankinson and A. M. Wade ( Statistics in Medicine 2009; 29:880-898): S.S. was funded by Asthma UK, Project ID 05/005. [ABSTRACT FROM AUTHOR]

Objectives: Native Andean ancestry gives partial protection from reduced birthweight at high altitude in the Andes compared with European ancestry. Whether Andean ancestry is also associated with body proportions and greater postnatal body size at altitude is unknown. Therefore, we tested whether a greater proportion of Andean ancestry is associated with stature and body proportions among Peruvian children at high and low altitude., Methods: Height, head circumference, head-trunk height, upper and lower limb lengths, and tibia, ulna, hand and foot lengths, were measured in 133 highland and 169 lowland children aged 6 months to 8.5 years. For highland and lowland groups separately, age-sex-adjusted anthropometry z scores were regressed on the number of indigenous parental surnames as a proxy for Andean ancestry, adjusting for potential confounders (maternal age and education, parity, altitude [highlands only])., Results: Among highland children, greater Andean ancestry was negatively associated with stature and tibia, ulna, and lower limb lengths, independent of negative associations with greater altitude for these measurements. Relationships were strongest for tibia length: each additional Andean surname or 1,000 m increase at altitude among highland children was associated with 0.18 and 0.65 z score decreases in tibia length, respectively. Anthropometry was not significantly associated with ancestry among lowland children., Conclusions: Greater Andean ancestry is associated with shorter stature and limb measurements at high but not low altitude. Gene-environment interactions between high altitude and Andean ancestry may exacerbate the trade-off between chest dimensions and stature that was proposed previously, though we could not test this directly., (© 2015 Wiley Periodicals, Inc.)

Background: The causes of the "dual burden" of stunting and obesity remain unclear, and its existence at the individual level varies between populations. We investigate whether the individual dual burden differentially affects low socioeconomic status Peruvian children from contrasting environments (urban lowlands and rural highlands), and whether tibia length can discount the possible autocorrelation between adiposity proxies and height due to height measurement error., Methods: Stature, tibia length, weight, and waist circumference were measured in children aged 3-8.5 years (n = 201). Height and body mass index (BMI) z scores were calculated using international reference data. Age-sex-specific centile curves were also calculated for height, BMI, and tibia length. Adiposity proxies (BMI z score, waist circumference-height ratio (WCHtR)) were regressed on height and also on tibia length z scores., Results: Regression model interaction terms between site (highland vs. lowland) and height indicate that relationships between adiposity and linear growth measures differed significantly between samples (P < 0.001). Height was positively associated with BMI among urban lowland children, and more weakly with WCHtR. Among rural highland children, height was negatively associated with WCHtR but unrelated to BMI. Similar results using tibia length rather than stature indicate that stature measurement error was not a major concern., Conclusions: Lowland and rural highland children differ in their patterns of stunting, BMI, and WCHtR. These contrasts likely reflect environmental differences and overall environmental stress exposure. Tibia length or knee height can be used to assess the influence of measurement error in height on the relationship between stature and BMI or WCHtR., (Copyright © 2014 Wiley Periodicals, Inc.)

Associations between season of birth and body size, morbidity, and mortality have been widely documented, but it is unclear whether different parts of the body are differentially sensitive, and if such effects persist through childhood. This may be relevant to understanding the relationship between early life environment and body size and proportions. We investigated associations between birth month and anthropometry among rural highland (n = 162) and urban lowland (n = 184) Peruvian children aged 6 months to 8 years. Stature; head-trunk height; total limb, ulna, tibia, hand, and foot lengths; head circumference; and limb measurements relative to head-trunk height were converted to internal age-sex-specific z scores. Lowland and highland datasets were then analyzed separately for birth month trends using cosinor analysis, as urban conditions likely provide a more consistent environment compared with anticipated seasonal variation in the rural highlands. Among highland children birth month associations were significant most strongly for tibia length, followed by total lower limb length and stature, with a peak among November births. Results were not significant for other measurements or among lowland children. The results suggest a prenatal or early postnatal environmental effect on growth that is more marked in limb lengths than trunk length or head size, and persists across the age range studied. We suggest that the results may reflect seasonal variation in maternal nutrition in the rural highlands, but other hypotheses such as variation in maternal vitamin D levels cannot be excluded., (Copyright © 2014 Wiley Periodicals, Inc.)

Objectives: The relative influences of hypoxia and other environmental stressors on growth at altitude remain unclear. Previous work demonstrated an association between peripheral arterial oxygen saturation (Sp O2 ) and anthropometry (especially tibia length) among Tibetan and Han children at altitude. We investigated whether similar associations exist among Andeans, and the patterning of associations between Sp O2 and anthropometry., Methods: Stature, head-trunk height, total upper and lower limb lengths, zeugopod (ulna and tibia) and autopod (hand and foot) lengths were measured in Peruvian children (0.5-14 years) living at >3000 m altitude. Sp O2 was measured by pulse oximetry. Anthropometry was converted to internal z scores. Correlation and multiple regression were used to examine associations between anthropometry z scores and Sp O2 , altitude, or Sp O2 adjusted for altitude since altitude is a major determinant of variation in Sp O2 ., Results: Sp O2 and altitude show weak, significant correlations with zeugopod length z scores and still weaker significant correlations with total upper and lower limb length z scores. Correlations with z scores for stature, head-trunk height, or autopod lengths are not significant. Adjusted for altitude, there is no significant association between anthropometry and Sp O2 ., Conclusions: Associations between Sp O2 or altitude and total limb and zeugopod length z scores exist among Andean children. However, the relationships are relatively weak, and while the relationship between anthropometry and altitude may be partly mediated by Sp O2, other factors that covary with altitude (e.g., socioeconomic status, health) are likely to influence anthropometry. The results support suggestions that zeugopod lengths are particularly sensitive to environmental stressors., (Copyright © 2013 Wiley Periodicals, Inc.)

Catecholamines modulate the production of inflammatory mediators by macrophages in an autocrine/paracrine manner. They also tune β2-adrenoceptor expression. Glucocorticoids influence catecholamine metabolism and adrenoceptor expression in many cell types. We hypothesized that adrenal hormones affect the production of tumour necrosis factor-α (TNF-α) and NO by macrophages by altering the modulatory influence of catecholamines. To prove the hypothesis, peritoneal exudate macrophages from propranolol-treated non-operated and adrenalectomized rats and from corticosterone-supplemented adrenalectomized rats were examined for lipopolysaccharide-stimulated NO and TNF-α production in vitro and for expression of β2-adrenoceptors and major catecholamine-metabolizing enzymes. Glucocorticoid deprivation increased NO production by macrophages, whereas 4 days of propranolol treatment was ineffective in this respect. However, propranolol treatment, via β2-adrenoceptor blockade, increased production of TNF-α by macrophages in both non-operated and adrenalectomized rats (showing dramatically enhanced TNF-α production due to a lack of circulating glucocorticoids) for the same value. The expression of β2-adrenoceptor was increased in peritoneal macrophages that were freshly isolated from non-operated, propranolol-treated and adrenalectomized rats (due to adrenal catecholamine deficiency). Propranolol did not affect macrophage β2-adrenoceptor expression in adrenalectomized rats. Given that propranolol increased the density of macrophage tyrosine hydroxylase expression only in non-operated rats and affected the mRNA expression of monoamine oxidase-A in neither non-operated nor adrenalectomized animals, a significant influence of propranolol on peritoneal exudate cell noradrenaline content was found only in non-operated rats. A lack of circulating adrenal hormones also affected noradrenaline metabolism and content in peritoneal exudate cells including macrophages. Collectively, despite differences in the abundance of macrophage catecholamine-β2-adrenoceptor system components and in the TNF-α response to lipopolysaccharide between adrenalectomized and non-operated rats, propranolol increased TNF-α production by the same amount in macrophages from these two groups of animals.