BackgroundLow serum levels of 25-hydroxyvitamin D3 are associated with an increased risk of respiratory tract infections (RTIs). Clinical trials with vitamin D3 against various infections have been carried out but data are so far not conclusive. Thus, there is a need for additional randomised controlled trials of effects of vitamin D3 on infections.ObjectiveTo investigate if supplementation with vitamin D3 could reduce infectious symptoms and antibiotic consumption among patients with antibody deficiency or frequent RTIs.DesignA double-blind randomised controlled trial.SettingKarolinska University Hospital, Huddinge.Participants140 patients with antibody deficiency (selective IgA subclass deficiency, IgG subclass deficiency, common variable immune disorder) and patients with increased susceptibility to RTIs (>4 bacterial RTIs/year) but without immunological diagnosis.InterventionVitamin D3 (4000 IU) or placebo was given daily for 1 year.Primary and secondary outcome measuresThe primary endpoint was an infectious score based on five parameters: symptoms from respiratory tract, ears and sinuses, malaise and antibiotic consumption. Secondary endpoints were serum levels of 25-hydroxyvitamin D3, microbiological findings and levels of antimicrobial peptides (LL-37, HNP1–3) in nasal fluid.ResultsThe overall infectious score was significantly reduced for patients allocated to the vitamin D group (202 points) compared with the placebo group (249 points; adjusted relative score 0.771, 95% CI 0.604 to 0.985, p=0.04).LimitationsA single study centre, small sample size and a selected group of patients. The sample size calculation was performed using p=0.02 as the significance level whereas the primary and secondary endpoints were analysed using the conventional p=0.05 as the significance level.ConclusionsSupplementation with vitamin D3 may reduce disease burden in patients with frequent RTIs.

OBJECTIVEOffspring of pregnancies affected by gestational diabetes mellitus (GDM) are at increased risk of the development of type 2 diabetes. However, the extent to which these dysmetabolic traits may be due to offspring and/or maternal adiposity is unknown. We examined body composition and associated cardiometabolic traits in 561 9- to 16-year-old offspring of mothers with GDM and 597 control offspring.RESEARCH DESIGN AND METHODSWe measured anthropometric characteristics; puberty status; blood pressure; and fasting glucose, insulin, C-peptide, and lipid levels; and conducted a DEXA scan in a subset of the cohort. Differences in the outcomes between offspring of mothers with GDM and control subjects were examined using linear and logistic regression models.RESULTSAfter adjustment for age and sex, offspring of mothers with GDM displayed higher weight, BMI, waist-to-hip ratio (WHR), systolic blood pressure, and resting heart rate and lower height. Offspring of mothers with GDM had higher total and abdominal fat percentages and lower muscle mass percentages, but these differences disappeared after correction for offspring BMI. The offspring of mothers with GDM displayed higher fasting plasma glucose, insulin, C-peptide, HOMA-insulin resistance (IR), and plasma triglyceride levels, whereas fasting plasma HDL cholesterol levels were decreased. Female offspring of mothers with GDM had an earlier onset of puberty than control offspring. Offspring of mothers with GDM had significantly higher BMI, WHR, fasting glucose, and HOMA-IR levels after adjustment for maternal prepregnancy BMI, and glucose and HOMA-IR remained elevated in the offspring of mothers with GDM after correction for both maternal and offspring BMIs.CONCLUSIONSIn summary, adolescent offspring of women with GDM show increased adiposity, an adverse cardiometabolic profile, and earlier onset of puberty among girls. Increased fasting glucose and HOMA-IR levels among the offspring of mothers with GDM may be explained by the programming effects of hyperglycemia in pregnancy.

Maternal supplementation with fish oil might have prophylactic potential for long-term prevention of asthma in offspring.

Rationale and objectivesThymic stromal lymphopoietin (TSLP), an epithelial upstream cytokine, initiates production of type-2 (T2) cytokines with eosinophilia and possibly airway hyperresponsiveness (AHR) in asthma.This study aimed to determine whether tezepelumab (a human monoclonal antibody targeting TSLP) decreases AHR and airway inflammation in patients with symptomatic asthma on maintenance treatment with inhaled corticosteroids.Methods and measurementsIn this double-blind, placebo-controlled randomised trial adult patients with asthma and AHR to mannitol received either 700 mg tezepelumab or placebo intravenously at 4-week intervals for 12 weeks. AHR to mannitol was assessed, and a bronchoscopy was performed at baseline and after 12 weeks. The primary outcome was the change in AHR from baseline to week-12 and secondary outcomes were changes in airway inflammation.ResultsForty patients were randomised to receive either tezepelumab (n=20) or placebo (n=20). The mean change in PD15 with tezepelumab was 1.9 DD (95% CI 1.2 to 2.5) versus 1·0 (95% CI 0.3 to 1.6) with placebo; p=0.06. Nine (45%) tezepelumab and three (16%) placebo patients had a negative PD15 test at week-12, p=0.04. Airway tissue and BAL eosinophils decreased by 74% (95% CI −53 to −86) and 75% (95% CI −53 to −86) respectively with tezepelumab compared with an increase of 28% (95% CI −39 to 270) and a decrease of 7% (95% CI −49 to 72) respectively with placebo, p=0.004 and p=0.01.ConclusionsInhibiting TSLP-signalling with tezepelumab reduced the proportion of patients with AHR and decreased eosinophilic inflammation in BAL and airway tissue.