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Background: Atopic dermatitis (AD) is the most common chronic inflammatory skin disease in infancy with a complex pathology. In adults, the clinical severity of AD has been associated with increases in T helper cell type (Th) 2, Th22, and Th17 serum markers, including high levels of CC chemokine ligand (CCL) 17 and CCL22 chemokines. Objective: To explore the possible association between serum chemokine levels and AD severity in infants with moderate-to-severe AD and elevated immunoglobulin E (IgE). subjects and methods: Serum samples (n = 41) obtained from a randomized, double- blind, and clinical dietary intervention study were used to study biomarkers in infants with AD. Baseline- and post-intervention samples (4 months) were used, six chemokines and nine ratios thereof were analyzed using Luminex and correlated to AD severity. In the initial study, the infants were randomized to receive extensively hydrolyzed wheybased formula without (control) or with short-chain galacto-oligosaccharides/long-chain fructo-oligosaccharides (9:1) and Bifidobacterium breve M-16V (active). results: 31 Infants up to 11 months of age, with an objective-SCORAD score (oSCORAD) ≥ 20 and elevated total-IgE and/or specific-IgE levels were included. In time, the median oSCORAD decreased in both groups by -8 (control, p < 0.05; active, p < 0.01). Irrespective of dietary intervention, several changes in Th2 chemokines(CCL17 and CCL22), inflammatory chemokine (CCL20), and the Th1 chemokine, CXC chemokine ligand (CXCL) 9, were detected over time. Overall CCL17 correlated to oSCORAD (r = 0.446, p < 0.01). After 4 months of dietary intervention, CXCL9 was higher (p < 0.01) in the active group compared with control [active, 2.33 (1.99-2.89); controls, 1.95 (1.77-2.43) log 10 median (range)]. In addition, a reduction in Th2/Th1 chemokine ratios for CCL17/CXCL9, CCL22/CXCL9, CCL20/CXCL10, and CCL20/ CXCL11 was detected associated with the active intervention. conclusion: While this study is small and exploratory in nature, these data contribute to immune biomarker profiling and understanding of AD in infants. [ABSTRACT FROM AUTHOR]

Background: The recommendations for the treatment of moderate persistent asthma in the Global Initiative for Asthma (GINA) guidelines for paediatric asthma are mainly based on scientific evidence extrapolated from studies in adults or on consensus. Furthermore, clinical decision-making would benefit from formal ranking of treatments in terms of effectiveness. Our objective is to assess all randomized trial-based evidence specifically pertaining to 5-18 year olds with moderate persistent asthma. Rank the different drug treatments of GINA guideline steps 3&4 in terms of effectiveness. Methods: Systematic review with network meta-analysis. After a comprehensive search in Central, Medline, Embase, CINAHL and the WHO search portal two reviewers selected RCTs performed in 4,129 children from 5-18 year old, with moderate persistent asthma comparing any GINA step 3&4 medication options. Further quality was assessed according the Cochrane Collaboration's tool and data-extracted included papers and built a network of the trials. Attempt at ranking treatments with formal statistical methods employing direct and indirect (e.g. through placebo) connections between all treatments. Results: 8,175 references were screened; 23 randomized trials (RCT), comparing head-to-head (n=17) or against placebo (n=10), met the inclusion criteria. Except for theophylline as add-on therapy in step 4, a closed network allowed all comparisons to be made, either directly or indirectly. Huge variation in, and incomplete reporting of, outcome measurements across RCTs precluded assessment of relative efficacies. Conclusion: Evidence-based ranking of effectiveness of drug treatments in GINA steps 3&4 is not possible yet. Existing initiatives for harmonization of outcome measurements in asthma trials need urgent implementation. [ABSTRACT FROM AUTHOR]

Background: Polychlorinated dioxins and -furans (PCDD/Fs) and polychlorinated-biphenyls (PCBs) are environmental toxicants that have been proven to influence thyroid metabolism both in animal studies and in human beings. In recent years polybrominated diphenyl ethers (PBDEs) also have been found to have a negative influence on thyroid hormone metabolism. The lower brominated flame retardants are now banned in the EU, however higher brominated decabromo-diphenyl ether (DBDE) and the brominated flame retardant hexabromocyclododecane (HBCD) are not yet banned. They too can negatively influence thyroid hormone metabolism. An additional brominated flame retardant that is still in use is tetrabromobisphenol-A (TBBPA), which has also been shown to influence thyroid hormone metabolism. Influences of brominated flame retardants, PCDD/F's and dioxin like-PCBs (dl-PCB's) on thyroid hormone metabolism in adolescence in the Netherlands will be presented in this study and determined if there are reasons for concern to human health for these toxins. In the period 1987-1991, a cohort of mother-baby pairs was formed in order to detect abnormalities in relation to dioxin levels in the perinatal period. The study demonstrated that PCDD/Fs were found around the time of birth, suggesting a modulation of the setpoint of thyroid hormone metabolism with a higher 3,3′, 5,5′tetrathyroxine (T4) levels and an increased thyroid stimulating hormone (TSH). While the same serum thyroid hormone tests (- TSH and T4) were again normal by 2 years of age and were still normal at 8-12 years, adolescence is a period with extra stress on thyroid hormone metabolism. Therefore we measured serum levels of TSH, T4, 3,3′,5-triiodothyronine (T3), free T4 (FT4), antibodies and thyroxine-binding globulin (TBG) in our adolescent cohort. Methods: Vena puncture was performed to obtain samples for the measurement of thyroid hormone metabolism related parameters and the current serum dioxin (PCDD/Fs), PCB and PBDE levels. Results: The current levels of T3 were positively correlated to BDE-99. A positive trend with FT4 and BDE-99 was also seen, while a positive correlation with T3 and dl-PCB was also seen. No correlation with TBG was seen for any of the contaminants. Neither the prenatal nor the current PCDD/F levels showed a relationship with the thyroid parameters in this relatively small group. Conclusion: Once again the thyroid hormone metabolism (an increase in T3) seems to have been influenced by current background levels of common environmental contaminants: dl-PCBs and BDE-99. T3 is a product of target organs and abnormalities might indicate effects on hormone transporters and could cause pathology. While the influence on T3 levels may have been compensated, because the adolescents functioned normal at the time of the study period, it is questionable if this compensation is enough for all organs depending on thyroid hormones. [ABSTRACT FROM AUTHOR]

Background: Asthma is a difficult diagnosis to establish in preschool children. A few years ago, our group presented a prediction rule for young children at risk for asthma in general practice. Before this prediction rule can safely be used in practice, cross-validation is required. In addition, general practitioners face many therapeutic management decisions in children at risk for asthma. The objectives of the study are: (1) identification of predictors for asthma in preschool children at risk for asthma with the aim of cross-validating an earlier derived prediction rule; (2) compare the effects of different treatment strategies in preschool children. Design: In this prospective cohort study one to five year old children at risk of developing asthma were selected from general practices. At risk was defined as 'visited the general practitioner with recurrent coughing (≥ 2 visits), wheezing (≥ 1) or shortness of breath (≥ 1) in the previous 12 months'. All children in this prospective cohort study will be followed until the age of six. For our prediction rule, demographic data, data with respect to clinical history and additional tests (specific immunoglobulin E (IgE), fractional exhaled nitric oxide (FENO), peak expiratory flow (PEF)) are collected. History of airway specific medication use, symptom severity and healthrelated quality of life (QoL) are collected to estimate the effect of different treatment intensities (as expressed in GINA levels) using recently developed statistical techniques. In total, 1,938 children at risk of asthma were selected from general practice and 771 children (40%) were enrolled. At the time of writing, follow-up for all 5-year olds and the majority of the 4-year olds is complete. The total and specific IgE measurements at baseline were carried out by 87% of the children. Response rates to the repeated questionnaires varied from 93% at baseline to 73% after 18 months follow-up; 89% and 87% performed PEF and FENO measurements, respectively. Discussion: In this study a prediction rule for asthma in young children, to be used in (general) practice, will be cross-validated. Our study will also provide more insight in the effect of treatment of asthma in preschool children. [ABSTRACT FROM AUTHOR]

Aim: The aim of the study was to assess, in a randomised, controlled design, the efficacy of different strategies to improve childhood asthma management. Method: Three interventions directed to three groups of general practitioners were compared: Group A - dissemination of a guideline; Group B - guideline dissemination plus an educational session; Group C - guideline dissemination, educational session, plus individualised treatment advice based on airway hyperresponsiveness (AHR) and symptoms. Efficacy of the three strategies was assessed by evaluating change in AHR in 362 children after one year. Results: The overall between-group effect of the severity of AHR was not significantly different (P=0.09). In Groups A and C an improvement was seen in nocturnal symptoms (P=0.02) and in Group C an improvement was seen in the prescription of inhaled corticosteroids (P=0.03). Conclusion: In this study, the combined implementation strategy did not show a clear improvement in the management of children with asthma in general practice. [ABSTRACT FROM AUTHOR]

In a general practice based population 76% of 530 children inhaling asthma medication inhaled correctly. However, important differences among inhalers were found. Children with a pressurized metered-dose inhaler without a spacer device performed worst, with only 22% inhaling without essential errors. At a second evaluation of the inhaler technique, one year after the first assessment, performances with a new device were more often incorrect versus the unchanged devices (21.1% and 10.8%, respectively; p = 0.01). Providing children with a new device should be carefully controlled over time especially because these children are error prone. [ABSTRACT FROM AUTHOR]

Little information is available about the role of skeletal muscle strength, including inspiratory and peripheral muscles, in patients with cystic fibrosis (CF). In this study, we evaluated inspiratory and peripheral muscle strength and their relationship with nutritional status and pulmonary function. We assessed forced expiratory volume in one second (FEV[sub 1]), inspiratory muscle strength (Pimax), peripheral muscle strength of the knee extensors and elbow flexors, body mass index (BMI), and lean body mass (LBM) in 22 patients in a stable condition. Mean (SD) age was 19 (5) years; FEV[sub 1] was 62 (28) percent predicted; inspiratory muscle strength was 118 (23) percent predicted; knee extensor strength was 80 (23) percent predicted; and elbow flexor strength 76 (21) percent predicted. Mean (SD) BMI was 19.5 (2.8) kg/m[sup 2] and LBM was 46.4 (10) kg. FEV[sub 1] (percent predicted) was significantly correlated with percent predicted inspiratory muscle strength (r = 0.53; p = 0.011), percent predicted knee extensor strength (r = 0.70, p < 0.001 ), and percent predicted elbow flexor strength (r = 0.62, p = 0.002). These results show that, despite a moderate relationship with FEV[sub 1], inspiratory muscle strength was preserved in our CF patients. Peripheral muscle strength was reduced in those patients with airflow obstruction. Future intervention should focus on the influence of reduced peripheral muscle strength on exercise performance in CF patients. [ABSTRACT FROM AUTHOR]