Characterization of the L-Arginine/Nitric Oxide Pathway and Oxidative Stress in Pediatric Patients with Atopic Diseases.

INTRODUCTION: L-Arginine (Arg) is a semi-essential amino acid. Constitutive and inducible nitric oxide synthase (NOS) isoforms convert Arg to nitric oxide (NO), a potent vaso- and bronchodilator with multiple biological functions. Atopic dermatitis (AD) and bronchial asthma (BA) are atopic diseases affecting many children globally. Several studies analyzed NO in airways, yet the systemic synthesis of NO in AD and BA in children with BA, AD or both is elusive. METHODS: In a multicenter study, blood and urine were obtained from 130 of 302 participating children for the measurement of metabolites of the Arg/NO pathway (BA 31.5%; AD 5.4%; AD + BA 36.1%; attention deficit hyperactivity disorder (ADHD) 12.3%). In plasma and urine amino acids Arg and homoarginine (hArg), both substrates of NOS, asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA), both inhibitors of NOS, dimethylamine (DMA), and nitrite and nitrate, were measured by gas chromatography-mass spectrometry. Malondialdehyde (MDA) was measured in plasma and urine samples to evaluate possible effects of oxidative stress. RESULTS: There were no differences in the Arg/NO pathway between the groups of children with different atopic diseases. In comparison to children with ADHD, children with AD, BA or AD and BA had higher plasma nitrite (p < 0.001) and nitrate (p < 0.001) concentrations, suggesting higher systemic NO synthesis in AD and BA. Urinary excretion of DMA was also higher (p = 0.028) in AD and BA compared to patients with ADHD, suggesting elevated ADMA metabolization. DISCUSSION/CONCLUSION: The Arg/NO pathway is activated in atopic diseases independent of severity. Systemic NO synthesis is increased in children with an atopic disease. Plasma and urinary MDA levels did not differ between the groups, suggesting no effect of oxidative stress on the Arg/NO pathway in atopic diseases.

25-Hydroxvitamin D concentrations are not lower in children with bronchial asthma, atopic dermatitis, obesity, or attention-deficient/hyperactivity disorder than in healthy children.

Vitamin D (vitD) is involved in immune regulation, and its receptor has been identified in several tissues including lung, adipose tissue, brain, and skin. Based on these observations, it has been suggested that vitD has an essential role not only in bone metabolism but also in other diseases such as atopic dermatitis (AD), bronchial asthma (BA), attention-deficit/hyperactivity disorder (ADHD), and obesity because the affected tissues express vitD receptors. Furthermore, obesity, AD, and BA are regarded as inflammatory diseases. Therefore, we hypothesized that vitD concentrations are lower in children with AD, BA, ADHD, and obesity compared to healthy children. We measured 25-hydroxyvitamin D concentrations in 235 children (60% boys, age 9.3±1.7years) with obesity, BA, AD, or ADHD and compared them to those of 3352 children from a healthy population. Additionally, parathyroid hormone was measured in the children with obesity, ADHD, BA, and AD. VitD concentrations were not lower in children with obesity, ADHD, BA, and AD compared to healthy children. In multiple regression analyses adjusted to migration background, time period of blood sample, age, and sex, VitD levels correlated significantly with the severity of AD measured by SCORing Atopic Dermatitis index and attention deficit measured by Conners questionnaire in ADHD. VitD levels were not linked to hyperactivity in ADHD, the severity of BA measured as forced expiration volume in the first second, or body mass index standard deviation score. Parathyroid hormone was not associated with the activity of any analyzed disease. In conclusion, most of our findings do not support the hypothesis that vitD is involved in the pathogenesis of these entities.

Thyroid Hormone Status in Overweight Children with Attention Deficit/Hyperactivity Disorder.

BACKGROUND: There is an ongoing discussion whether thyroid hormones are involved in the development and course of attention deficit/hyperactivity disorder (ADHD). Since obesity is associated with both higher thyroid-stimulating hormone (TSH) and free triiodothyronine (fT3) concentrations and increased rates of ADHD, we hypothesized that overweight children with ADHD show higher TSH and fT3 concentrations compared to overweight children without ADHD. METHODS: TSH, fT3, fT4, and leptin levels were analyzed in 230 children (60.9% boys, 9.3 ± 1.7 years old, 35.7% migration background). The children were divided into four groups (I = 26 overweight children with ADHD, II = 56 normal-weight children with ADHD, III = 66 overweight children without ADHD, and IV = 82 normal-weight children without ADHD). Severity of ADHD was determined by the parent version of the Connors 3® rating scales. RESULTS: Overweight children with ADHD did not differ significantly from overweight children without ADHD with respect to TSH, fT3, or fT4 concentrations. Comparing the thyroid hormones between the four groups also demonstrated no significant differences for TSH and fT4 concentrations. fT3 concentrations were significantly higher in normal-weight children with ADHD compared to normal-weight children without ADHD. Inattention and hyperactivity/impulsivity scores were not significantly related to TSH or fT3 in multiple regression analyses adjusted for age, gender, and migration background. In these analyses, TSH was associated with BMI SDS (ß coefficient 0.19 ± 0.12, p = 0.002) and leptin (exp[ß coefficient] 1.87 ± 1.36, p < 0.001). fT3 (ß coefficient 0.06 ± 0.05, p = 0.009) and leptin (exp[ß coefficient] 1.17 ± 1.13, p = 0.009) were also associated with BMI SDS. CONCLUSIONS: Our findings confirm the relation between overweight and thyroid hormones but point against the hypothesis that thyroid hormones might link overweight and ADHD in children.