Peanut components measured by ISAC: comparison with ImmunoCap and clinical relevance in peanut allergic children.

BACKGROUND: Specific IgE (sIgE) against the peanut component Arachis hypogaea (Ara h) 2 has been shown to be the most important allergen to discriminate between peanut allergy and peanut tolerance. Several studies determined sIgE cut off values for Ara h 2, determined by singleplex measurements. However, cut off values for Ara h 2 from multiplex arrays are less well defined. The aim of this study was to evaluate the correlation between Ara h 2 sIgE determined by singleplex versus multiplex measurements and to assess the diagnostic value of the different peanut components included in Immuno Solid-phase Allergen Chip (ISAC) multiplex analysis in children with a suspected peanut allergy. METHODS: In this retrospective study we analyzed Ara h 2 sIgE values with singleplex Fluorescence Enzyme Immunoassay (FEIA, ImmunoCap) and multiplex microarray (ISAC) measurements in 117 children with a suspected peanut allergy. Also, other peanut components measured by ISAC were analyzed. Double blinded placebo controlled oral food challenges were used as golden standard. RESULTS: Among all studied peanut components FEIA Ara h 2 sIgE showed the highest area under the curve (AUC, 0.922), followed by ISAC Ara h 6 and Ara h 2 sIgE with AUCs of respectively 0.906 and 0.902. Best cut off values to diagnose peanut allergy were 4.40 kU/l for FEIA Ara h 2 sIgE and, 7.43 ISU and 8.13 ISU for respectively Ara h 2 and Ara h 6 sIgE in ISAC microarray. Ara h 2 sIgE determined in FEIA and ISAC showed a good correlation (r = 0.88; p < 0.01). CONCLUSION: Ara h 6 and Ara h 2 sIgE in multiplex ISAC are both good predictors of clinical peanut allergy in Dutch children, and their performance is comparable to the use of Ara h 2 in singleplex FEIA. The simultaneous measurement of different peanut components using ISAC is an advantage and clinically useful to detect peanut allergic children that are Ara h 2 negative but sensitized to other peanut proteins such as Ara h 6.

Use of the Control of Allergic Rhinitis and Asthma Test (CARATkids) in children and adolescents: Validation in Dutch.

BACKGROUND: Allergic rhinitis and asthma are common and closely related diseases. Recently, a Portuguese questionnaire has been developed 'The Control of Allergic Rhinitis and Asthma Test' (CARATkids) that measures disease control of both diseases in children. This study aims to validate the CARATkids in Dutch children and for the first time in adolescents and, in addition, to calculate the minimal clinically important difference (MCID). METHODS: A prospective observational study was conducted in an outpatient clinic. After translation of the CARATkids from Portuguese to Dutch, patients (6-18 years) with asthma or asthma and allergic rhinitis completed the CARATkids, Asthma Control Test, and visual analog scale questionnaire three times. Baseline characteristics, mean scores, internal consistency, test-retest reliability, cross-sectional and longitudinal validity, discriminative properties, responsiveness, and MCID of the CARATkids were assessed. RESULTS: A total of 111 patients were included. In total, 86% and 79%, respectively, completed the questionnaires at the second and third visits. All children had asthma, and 85% had concomitant allergic rhinitis. The internal consistency was good with all expected a priori correlations met. CARATkids scores were higher in patients with uncontrolled asthma and patients with moderate-severe rhinitis compared to better controlled subjects. Patients with a variable asthma control had significantly higher scores during periods of uncontrolled asthma. Also the Guyatt's responsiveness index was good. The MCID was 2.8. CONCLUSIONS: The CARATkids questionnaire is a reliable and valid tool to assess allergic rhinitis and asthma control among Dutch children. The tool can be used in adolescents.

Mono-sensitisation to peanut component Ara h 6: a case series of five children and literature review.

UNLABELLED: Here, we summarise the current clinical knowledge on Ara h 6 sensitisation and clinical relevance of this sensitisation pattern using five illustrative clinical cases. The literature search yielded a total of 166 papers, and an additional relevant article was found by 'snowballing'. A total of ten articles were considered relevant for this review. Most studies included patients with a sensitisation to Ara h 6 and cosensitisation to Ara h 2. Only three studies showed patients with a mono-sensitisation to Ara h 6. This illustrates that Ara h 6 mono-sensitisation has been neglected in literature. We present a case series of five children with sensitisation to peanut component Ara h 6. Only one of these five patients showed Ara h 8 cosensitivity. Three out of the five children had a positive double-blind placebo-controlled food challenge (DBPCFC), with moderate to strong reactions. CONCLUSION: A mono-sensitisation to peanut component Ara h 6 is uncommon but can cause severe allergic reactions. Therefore, the determination of sIgE to Ara h 6 is warranted in patients with a suspected peanut allergy, especially in the absence of sensitisation to Ara h 1, 2, 3 and 9. WHAT IS KNOWN: • Peanut allergy is common and can cause severe allergic reactions. • The diagnostics of peanut allergy has recently improved with the use of component resolved diagnosis What is new: • A mono-sensitisation to peanut component Ara h 6 is uncommon, but can cause severe allergic reactions • Determination of sIgE to Ara h 6 is warranted in patients with a suspected peanut allergy, especially in the absence of sensitisation to Ara h 1, 2, 3 and 9.

Food intake of children with short stature born small for gestational age before and during a randomized GH trial.

Parents of short children born SGA often report that their children have a serious lack of appetite and a low food intake. In this study we investigated food intake, by using a standardized 7-day food questionnaire, in 88 short SGA children before start of GH treatment. The intake was compared with the recommended daily intake (RDI) of age-matched children. We also compared the food intake of GH-treated children (n=62) with randomized controls (n=26) after 1 year of GH treatment. In addition, we evaluated the effect of food intake and GH treatment on body composition and serum levels of IGF-I, IGFBP-3 and leptin. Our study shows that caloric intake, fat and carbohydrate intake of short SGA children aged 5.9 (1.6) years was significantly lower compared to the RDI for age-matched children. One year of GH treatment resulted in a significant increase of caloric, fat, carbohydrate and protein intake compared to baseline. Compared to randomized controls, caloric, carbohydrate and protein intake increased significantly after 1 year of GH treatment. Short SGA children had significantly lower SDS scores for LBM, fat mass, skinfold (SF) and BMI compared to age-matched references. They also had significantly lower serum IGF-I, IGFBP-3 and leptin levels. GH treatment resulted in a significant increase of height, LBM, BMI, IGF-I and IGFBP-3 SDS and a significant decrease of SF SDS and leptin SDS. In conclusion, our study shows that short SGA children have indeed a lower food intake than age-matched controls. During GH treatment the food intake increased significantly compared to baseline in contrast to the randomized control group.

Reduced insulin sensitivity and the presence of cardiovascular risk factors in short prepubertal children born small for gestational age (SGA).

BACKGROUND: Epidemiological studies have shown that the metabolic syndrome, a combination of type 2 diabetes mellitus, hypertension, dyslipidaemia and a high body mass index (BMI), occurs more frequently among adults who were born with a low birth weight. Because insulin is thought to play a key role in the pathogenesis of this syndrome we investigated insulin sensitivity and risk factors for cardiovascular disease in short prepubertal children born small for gestational age (SGA). PATIENTS AND METHODS: Frequently sampled intravenous glucose tolerance tests (FSIGT) were performed in 28 short prepubertal children born SGA. Short stature was defined as a height < -2SD. SGA was defined as a birth length and/or a birth weight for gestational age < -2SD. Twelve short children born appropriate for gestational age (AGA) were used as controls for the FSIGT's results only. AGA was defined as a birth weight and/or birth length for gestational age > -2SD. In short SGA children, blood pressure (BP), fasting levels of serum free fatty acids (FFA), triglycerides (TG), total cholesterol (TC), high-density lipoprotein (HDL) cholesterol and low-density lipoprotein (LDL) were measured and compared to reference values. RESULTS: Mean insulin sensitivity (Si) level in short SGA children was significantly reduced to 38% of the mean Si level measured in short AGA controls (P = 0.004). Mean acute insulin response (AIR) was significantly higher in SGA children compared to short AGA controls (P < 0.001). Differences in Si and AIR between the two groups remained significant after adjusting for age and BMI (P < 0.001 and P = 0.003, respectively). The mean (SD) systolic BP SDS was 1.3 (1,1), being significantly higher than zero. Mean fasting serum levels of FFA, TC, TG, HDL and LDL were all within the normal range. However, 6 of the 28 SGA children had serum FFA levels above the normal range. Cardiovascular risk factors could statistically be represented in two clusters. Both clusters played a significant role in the development of insulin insensitivity (1/Si). CONCLUSION: Although the metabolic syndrome has been described in adulthood, our study showed that risk factors for the development of type 2 diabetes mellitus and cardiovascular disease are already present during childhood in short prepubertal children born SGA, suggesting a pretype 2 diabetes mellitus phenotype.

Small for gestational age (SGA): endocrine and metabolic consequences and effects of growth hormone treatment.

Several studies have demonstrated an association between low birth weight and impaired insulin sensitivity or even type 2 diabetes mellitus (DM2) in later life. Growth hormone (GH) is known to increase fasting and postprandial insulin levels. For that reason concern has been expressed regarding possible detrimental effects of GH therapy in children born SGA. In a Dutch trial the possible side effects of GH therapy on carbohydrate metabolism were assessed in short children born SGA after 6 years and at 6 months after discontinuation of GH therapy. This study included 79 prepubertal short children born SGA, participating in a multicenter double-blind, randomized, dose-response GH trial. Inclusion criteria were: 1) birth length SDS below -1.88, 2) age 3-11 years in boys and 3-9 years in girls, 3) height SDS < -1.88, 4) no spontaneous catch-up growth, and 5) an uncomplicated neonatal period. Mean (SD) value for age was 7.3 (2.1) years, birth length SDS -3.6, height SDS -3.0 (0.7) and BMI SDS -1.2 (1.3). All children were randomly assigned to either group A (n = 41) using 1 mg GH/m2/day or group B (n = 38) using 2 mg/m2/ d/ay (approximately 0.1 or 0.2 IU/kg/d, respectively). Standard oral glucose tolerance tests (OGTTs) were performed before and during 6 years of GH therapy and 6 months after discontinuation of GH therapy. Before GH therapy 8% of the children had impaired glucose tolerance (IGT) according to criteria of the WHO. After 6 years of GH therapy, IGT was found in 4% and after stopping GH in 10%. Mean fasting glucose increased significantly with 0.5 mMol/l after 1 year of GH therapy, without a further increase thereafter. GH therapy induced considerably higher fasting and glucose-stimulated insulin levels. None of the observed changes were different between the GH dosage groups. Children who remained prepubertal had similar glucose and insulin levels compared to children who entered puberty. HbA1c levels were always in the normal range and none of the children developed diabetes mellitus. After discontinuation of GH therapy the mean serum glucose levels remained normal and the mean serum insulin levels decreased significantly, to normal age reference values. Before the start of GH the mean systolic blood pressure was significantly higher compared to age-matched peers, whereas during GH therapy a significant decline in mean systolic blood pressure occurred, which remained similar after discontinuation of GH treatment. In conclusion, continuous, long-term GH therapy in short children born SGA has no adverse effects on glucose levels, even with GH dosages up to 2 mg/m2/day. However, as has been reported in other patient groups, GH induced higher fasting and glucose-stimulated insulin levels, indicating insulin resistance. After discontinuation of GH, serum insulin levels declined to normal age-matched reference levels. Since impaired insulin sensitivity and DM2 have been demonstrated in relatively young patients born SGA, long-term follow-up of children born SGA is advised, also after discontinuation of GH therapy.

GH treatment and its effect on bone mineral density, bone maturation and growth in short children born small for gestational age: 3-year results of a randomized, controlled GH trial.

BACKGROUND: To investigate in a group of short children born small for gestational age (SGA), the effects of 3 years of GH treatment vs. no treatment on bone age (BA), height and bone mineral density (BMD). Also, to evaluate the influence of the severity of growth retardation at start and the GH dose on the gain in height. PATIENTS AND METHODS: The study design was an open-labelled, controlled multicentre GH study for 3 years. Non-GH-deficient (GHD) children (n = 87) were randomized to either a GH group (n = 61) or an untreated control group (n = 26). In addition, 12 SGA children had GHD (GHD group) and were treated in parallel. Both the GH and the GHD group were treated with a GH dose of 33 microg/kg/day. BMD was evaluated using dual energy X-ray absorptiometry (DEXA). In addition, data of our first GH trial in which short SGA children were treated with a GH dose of 66 microg/kg/day (n = 24) were used for comparison of height gain. RESULTS: In contrast to the control group, the GH group showed a significant increase in height (P < 0.001), as did the parallel GHD group. Bone maturation [delta bone age (BA)/delta calendar age (CA)] increased significantly during the first 2 years of GH treatment but slowed-down thereafter. The 3-year deltaBA/deltaCA ratio correlated significantly with the gain in height (r = 0.6, P < 0.001). At start, mean BMD SDS and mean BMAD SDS were significantly lower than zero. During GH treatment both increased impressively (P < 0.001). The gain in height of children with severe short stature at start (< or = -3.00 SDS), did not differ between those receiving either a GH dose of 33 or 66 microg/kg/day. CONCLUSION: Three years of GH treatment in short children born SGA results in a normalization of height during childhood. Also, bone maturation increased proportionately to the height gain. At start, mean values of BMD and BMAD were significantly reduced but normalized during GH treatment. We did not find an indication to treat very short SGA children (H SDS < or = -3.00) with a higher GH dose. We rather suggest to start GH treatment at an early age in order to achieve a normal height before puberty starts.

MRI findings of the pituitary gland in short children born small for gestational age (SGA) in comparison with growth hormone-deficient (GHD) children and children with normal stature.

BACKGROUND: Disturbances in the GH/IGF-I axis are reported in 25-60% of short children born small for gestational age (SGA). We hypothesized that these abnormalities might be related to abnormalities in the pituitary region. Therefore, the results of magnetic resonance imaging (MRI) of short SGA children were compared to MRI results of other groups of short children and to normal controls. PATIENTS AND METHODS: MRI was performed in four groups of short children: SGA children without GH deficiency (SGA group; n = 17), SGA children with isolated GH deficiency (SGA + IGHD group; n = 10), non-SGA children with isolated GH deficiency (IGHD group; n = 24) and non-SGA children with multiple pituitary hormone deficiencies (MPHD group; n = 15). MRI was also performed in children with normal stature (control group; n = 13). Pituitary height (PH) and thickness of the pituitary stalk (PS) were measured and their relationship with the maximum GH peak during a GH stimulation test, serum IGF-I and IGFBP-3 levels was evaluated. RESULTS: Short SGA children either with or without IGHD did not show major anatomical abnormalities in the hypothalamic-pituitary region in contrast to 58% of the non-SGA IGHD children and 87% of the MPHD children who had anatomical abnormalities. PH in SGA children without GHD was normal whereas it was significantly lower in SGA children with IGHD. The lowest PHs were measured in non-SGA children with MPHD. A moderate decrease in PH was associated with significantly lower maximum serum GH peaks and lower serum IGF-I and IGFBP-3 levels. CONCLUSION: Measuring PHs in children with less severe GHD, who underwent MRI as part of the diagnostic process, might support the diagnosis of GHD even in the absence of anatomical abnormalities. Our study demonstrates that there is no indication to perform MRI of the pituitary region in short children born SGA without GHD.