There is a substantial disagreement between SPT and sIgE for diagnosing allergic sensitization in young children, which increases with age for food sensitization. Choice of assessment method therefore has major impact on results with wide implications for both clinical practice and research.

The miRNA hsa-miR-197-3p at 3 months was the strongest predictor of residual beta cell function 1 year after diagnosis in children with type 1 diabetes mellitus.

The objective of this study was to identify circulating miRNAs affected by disease duration in newly diagnosed children with type 1 diabetes. Forty children and adolescents from The Danish Remission Phase Cohort were followed with blood samples drawn at 1, 3, 6, 12 and 60 months after diagnosis. Pancreatic autoantibodies were measured at each visit. Cytokines were measured only the first year. miRNA expression profiling was performed by RT-qPCR and quantified for 179 human plasma miRNAs. The effect of disease duration was analyzed by mixed models for repeated measurements, adjusted for sex and age. Eight miRNAs (hsa-miR-10b-5p, hsa-miR-17-5p, hsa-miR-30e-5p, hsa-miR-93-5p, hsa-miR-99a-5p, hsa-miR-125b-5p, hsa-miR-423-3p and hsa-miR-497-5p) were found to significantly change expression (adjusted p-value < 0.05) with disease progression. Three pancreatic autoantibodies ICA, IA-2A, GADA65 and 4 cytokines IL-4, IL-10, IL-21, IL-22 were associated with the miRNAs at different time points. Pathway analysis revealed association with various immune-mediated signaling pathways. Eight miRNAs, involved in immunological pathways changed expression levels during the first five years after diagnosis in children with type 1 diabetes, and were associated with variations in cytokine and pancreatic antibodies, suggesting a possible effect on the immunological processes in the early phase of the disease.

Circulating microRNAs (miRNAs) have been implicated in several pathologies including type 1 diabetes. In the present study, we aimed to identify circulating miRNAs affected by disease duration in children with recent onset type 1 diabetes. Forty children and adolescents from the Danish Remission Phase Cohort were followed with blood samples drawn at 1, 3, 6, 12, and 60 months after diagnosis. Pancreatic autoantibodies were measured at each visit. Cytokines were measured only the first year. miRNA expression profiling was performed by RT-qPCR. The effect of disease duration was analyzed by mixed models for repeated measurements adjusted for sex and age. Eight miRNAs (hsa-miR-10b-5p, hsa-miR-17-5p, hsa-miR-30e-5p, hsa-miR-93-5p, hsa-miR-99a-5p, hsa-miR-125b-5p, hsa-miR-423-3p, and hsa-miR-497-5p) were found to significantly change in expression (adjusted p-value < 0.05) with disease progression. Three pancreatic autoantibodies, ICA, IA-2A, and GAD65A, and four cytokines, IL-4, IL-10, IL-21, and IL-22, were associated with the miRNAs at different time points. Pathway analysis revealed associations with various immune-mediated signaling pathways. Eight miRNAs that were involved in immunological pathways changed expression levels during the first five years after diagnosis and were associated with variations in cytokine and pancreatic antibodies, suggesting a possible effect on the immunological processes in the early phase of the disease.

AIMThe fixed combination of beclomethasone (BDP) and formoterol pressurized metered dose inhaler (pMDI) (Foster®, Chiesi Farmaceutici) is being developed in the lower strength (BDP/formoterol: 50/6 mg) to provide an appropriate dosage for children with asthma. The aim of this work was to investigate the systemic bioavailability of beclomethasone-17-monoproprionate (B17MP, the active metabolite of BDP) and formoterol after single inhalation of Foster® pMDI 50/6 mg vs. the free combination of BDP and formoterol pMDIs in asthmatic children. METHODSChildren aged 5-11 years old inhaled BDP 200 mg and formoterol 24 mg as fixed vs. free combination in an open label, randomized, two way crossover single dose study. Blood was collected pre-dose up to 8 h post-dose for pharmacokinetic evaluation (AUC(0,t), AUC(0,•), AUC(0,0.5 h, Cmax, tmax, t1/2). Pharmacodynamics included heart rate, plasma potassium, urinary glucose and cortisol excretion. Peak expiratory flow and adverse events were monitored. RESULTSTwenty subjects were evaluable. The systemic exposure of B17MP and formoterol administered as fixed combination did not exceed the free combination: B17MP AUC(0,t) (pg ml -1 h) ratio test : reference (90% CI), 0.81 (0.697, 0.948) and formoterol AUC(0,t) (pg ml -1 h) ratio test : reference 0.97 (0.85, 1.10). All pharmacokinetic and pharmacodynamic end points showed non-superiority in favour of the test drug. One adverse event (vertigo) occurred but was not considered treatment-related. CONCLUSIONBDP and formoterol pharmacokinetic and pharmacodynamic effects are non-superior after administration of the two actives as fixed vs. the free combination in 5-11-year-old asthmatic children. WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• The fixed combination of beclomethasone dipropionate and formoterol pMDI is marketed as Foster® 100/6 mg for use in adults with asthma. Foster® is now being developed in the lower strength (50/6 mg) to provide an appropriate dosage for children with asthma. WHAT THIS STUDY ADDS• This study demonstrates that beclomethasone dipropionate and formoterol pharmacokinetic and pharmacodynamic effects are non-superior after administration of the two actives as fixed vs. the free combination in asthmatic children aged 5-11 years.

The systemic exposure to the active ingredients of BDP/formoterol administered as DPI correlates inversely with age and body size suggesting that dry powder dosage regimens should be adjusted for age and body size to avoid high systemic drug levels in children.

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