Background New evidence supports the use of supplemental vitamin D in the prevention of exacerbation of asthma; however, the optimal posology to sufficiently raise serum levels while maximising adherence is unclear. The objective was to ascertain the efficacy of high-dose vitamin D 3 in increasing serum vitamin D in preschoolers with asthma and provide preliminary data on safety and efficacy outcomes. Methods We conducted a 7-month, triple-blind, randomised, placebo-controlled, pilot trial of children aged 1–5 years with viral-induced asthma. Participants were allocated to receive two oral doses of 100,000 IU vitamin D 3 (intervention) or identical placebo (control) 3.5 months apart, once in the fall and once in the winter. Serum 25-hydroxyvitamin D (25OHD) was measured by tandem mass spectrometry at baseline, 10 days, 3.5 months, 3.5 months + 10 days, and 7 months. The main outcome was the change in serum 25OHD from baseline (Δ25OHD) over time and at 3.5 and 7 months; other outcomes included the proportion of children with 25OHD ≥ 75 nmol/L, safety, and adverse event rates. Results Children ( N = 47) were randomised (intervention, 23; control, 24) in the fall. There was a significant adjusted group difference in the Δ25OHD (95% confidence interval) of 57.8 (47.3, 68.4) nmol/L, p < 0.0001), with a time ( p < 0.0001) and group*time interaction effect ( p < 0.0001), in favour of the intervention. A significant group difference in the Δ25OHD was observed 10 days after the first (119.3 [105.8, 132.9] nmol/L) and second (100.1 [85.7, 114.6] nmol/L) bolus; it did not reach statistical significance at 3.5 and 7 months. At 3.5 and 7 months, respectively, 63% and 56% of the intervention group were vitamin D sufficient (≥ 75 nmol/L) compared to 39% and 36% of the control group. Hypercalciuria, all without hypercalcaemia, was observed in 8.7% of intervention and 10.3% of control samples at any time point. Exacerbations requiring rescue oral corticosteroids, which appear as a promising primary outcome, occurred at a rate of 0.87/child. Conclusion Two oral boluses of 100,000 IU vitamin D 3, once in the fall and once in the winter, rapidly, safely, and significantly raises overall serum vitamin D metabolites. However, it is sufficient to maintain 25OHD ≥ 75 nmol/L throughout 7 months in only slightly more than half of participants. Trial registration ClinicalTrials.gov, NCT02197702 (23 072014). Registered on 23 July 2014. Electronic supplementary material The online version of this article (10.1186/s13063-019-3184-z) contains supplementary material, which is available to authorized users.

@ERSpublicationsThe incidence of children on montelukast with drug cessation due to neuropsychiatric adverse events was >10% http://ow.ly/nCGG30bgjpd ABSTRACT Although montelukast is generally well tolerated, postmarketing studies have reported serious neuropsychiatric adverse drug reactions (ADRs) leading to a United States Food and Drug Administration black box warning. The objective of this study was to determine the incidence of neuropsychiatric ADRs leading to discontinuation of montelukast in asthmatic children.We conducted a retrospective cohort study in children aged 1-17 years initiated on montelukast. In a nested cohort study, children initiated on montelukast as monotherapy or adjunct therapy to inhaled corticosteroids (ICS) were matched to those initiated on ICS monotherapy. A non-leading parental interview served to ascertain the occurrence of any ADRs with any asthma medication, and circumstances related to, and evolution of, the event.Out of the 106 participants who initiated montelukast, most were male (58%), Caucasian (62%) with a median (interquartile range) age of 5 (3-8) years. The incidence (95% CI) of drug cessation due to neuropsychiatric ADRs was 16 (10-26)%, mostly occurring within 2 weeks. Most frequent ADRs were irritability, aggressiveness and sleep disturbances. The relative risk of neuropsychiatric ADRs associated with montelukast versus ICS was 12 (2-90).In the real-life setting, asthmatic children initiated on montelukast experienced a notable risk of neuropsychiatric ADRs leading to drug cessation, that is significantly higher than that associated with ICS.

BackgroundWith several commercially available devices measuring respiratory impedance by oscillometry, the agreement between values obtained on different instruments or frequencies remains unclear. Our aim was to examine the agreement between resistance and reactance parameters on two oscillometry instruments using different waveforms.MethodsWe conducted a prospective cross-sectional study in asthmatic children aged 3–17 years. Reproducible oscillometry measurements were obtained in random order, by blinded operators, at three modes: 5–10–15–20–25 Hz (5–25 Hz) multifrequency mode on the MasterScreen impulse oscillometry system, and both 5–25 Hz multifrequency mode and 7 Hz monofrequency on the tremoFlo C-100 airwave sinusoidal system. Resistance, reactance and within-breath parameters were examined using the intraclass correlation coefficient (ICC), paired t-test, linear regression and Bland–Altman method.ResultsOf 50 participants, 44 and 38 completed between-device and within-frequency measurements, respectively. Between-device measurements at 5–25 Hz showed high (ICC 0.88–0.91) and good (ICC 0.69–0.87) agreement in resistance and reactance, respectively, but with an absolute within-patient difference (≥0.05 kPa·L−1·s−1) and proportional bias (≥30% per kPa·L−1·s−1) in all parameters and oscillatory frequencies, apart from resistance at 5 Hz. A significant proportional bias was documented in most within-breath parameters at 5 versus 7 Hz on tremoFlo.ConclusionObserved differences in resistance and reactance suggest the need for instrument- and frequency-specific paediatric normative values.