The diagnostic and prognostic power of the IDAA1c measure is kept but due to the higher Boost stimulation in the Danish cohort, the specificity of the formula is lower with the chosen limits for SCP (300 pmol/L) and IDAA1c ≤9, respectively.

We compared the clinical effect of the glucocorticoid budesonide delivered from two nebulizers Aiolos® and Pari LL® in 38 children less than 4 years of age (mean age, 20.2 months) with chronic wheeze. The design was a controlled, single‐blind, randomized, cross‐over, dose titration study. After a 1‐week run‐in, patients were randomized to treatment with 1 mg budesonide b.i.d. for 2 weeks from either an Aiolos® or a Pari LL® nebulizer. This was followed by a gradual dose reduction period during which the budesonide dose was reduced at 2‐week intervals until unacceptable asthma symptoms appeared or the placebo level was reached. The patient was then switched to budesonide 1 mg b.i.d. from the other nebulizer for 2 weeks, after which the dose was reduced at 2‐week intervals as described for the first period. Patients who completed the study on placebo for 2 weeks without deterioration of their asthma were not included in the statistical analysis. During Period # 1 the minimum effective dose of budesonide was 2 mg/day in 9 patients, 1 mg/day in 10 patients, and 0.5 mg/day in 13 patients. In Period #2 the corresponding figures were 14, 5, and 13 patients. Six patients were excluded after the first period because their asthma control did not deteriorate during dose reduction and when finishing on placebo for 2 weeks. For both nebulizers the reduction in budesonide dose was associated with a small increase in symptoms and use of rescue terbutaline. The mean dose of budesonide delivered to the patient by the Aiolos® was twice as large as that delivered by the Parl LL®: 26% vs. 13% of the nominal dose assessed by the filter method. Nevertheless, no statistically significant difference in clinical effect or mean minimal effective dose (1.1 mg for Aiolos® and 1.2 mg for Pari LL®) could be detected between the two nebulizers. No serious adverse events were observed. We conclude that the minimal effective dose of nebulized budesonide varies from 0.5 to 2.0 mg/day in young children with asthma. A higher drug delivery, as assessed by the filter method, does not necessarily result in better clinical control or lower minimal effective dose. Further studies are needed to assess whether this is due to insufficient sensitivity of the study design in detecting a difference in clinical effect, or whether measurements of drug delivery by the filter method do not reflect lung deposition or clinical effect in young children with wheezing. Pediatr Pulmonol. 1997;23:270–277. © 1997 Wiley‐Liss, Inc.

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The purpose of the present study is to explore the progression of type 1 diabetes (T1D) in Danish children 12 months after diagnosis using Latent Factor Modelling. We include three data blocks of dynamic paraclinical biomarkers, baseline clinical characteristics and genetic profiles of diabetes related SNPs in the analyses. This method identified a model explaining 21.6% of the total variation in the data set. The model consists of two components: (1) A pattern of declining residual β-cell function positively associated with young age, presence of diabetic ketoacidosis and long duration of disease symptoms (P = 0.0004), and with risk alleles of WFS1, CDKN2A/2B and RNLS (P = 0.006). (2) A second pattern of high ZnT8 autoantibody levels and low postprandial glucagon levels associated with risk alleles of IFIH1, TCF2, TAF5L, IL2RA and PTPN2 and protective alleles of ERBB3 gene (P = 0.0005). These results demonstrate that Latent Factor Modelling can identify associating patterns in clinical prospective data – future functional studies will be needed to clarify the relevance of these patterns.

The aim of this study was to evaluate if continuous treatment with budesonide or salmeterol influences the bronchodilator response to terbutaline in children with asthma; 23 children, aged 7 to 16 years (mean = 11 years), with mild asthma were treated with inhaled budesonide 100 micrograms b.i.d. and placebo for three weeks in a randomized, double blind crossover study. These treatments were followed by treatment with inhaled salmeterol 50 micrograms b.i.d. for 3 weeks. On the last day of each period a cumulative dose-response experiment with terbutaline in the doses 50, 100, 250 and 500 micrograms (cumulative dose 900 micrograms) was performed. Lung function was measured before and 20 min after each terbutaline inhalation. Baseline pulmonary functions after budesonide treatment were significantly higher than the baseline measured after the two other treatments (p < 0.05). After budesonide treatment, the dose-response curve was shifted vertically upwards but otherwise parallel to the dose-response curve after placebo. The increase from baseline after the first cumulative dose of terbutaline was significantly lower after salmeterol treatment than after the two other treatments (p < 0.01). Maximal lung functions after 900 micrograms terbutaline also differed significantly between the three dose-response days; budesonide being significantly higher and salmeterol significantly lower than placebo (p = 0.02 and p < 0.001, respectively). It is concluded that budesonide treatment does not enhance the brochodilator response to terbutaline. Further studies are needed to assess if long-term continuous salmeterol treatment reduces the response to terbutaline.