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Asthma is the most prevalent pediatric chronic disease. Bronchodilator drug response (BDR) and fractional exhaled nitric oxide (FeNO) are clinical biomarkers of asthma. Although DNA methylation (DNAm) contributes to asthma pathogenesis, the influence of DNAm on BDR and FeNO is scarcely investigated. This study aims to identify DNAm markers in whole blood associated either with BDR or FeNO in pediatric asthma. We analyzed 121 samples from children with moderate-to-severe asthma. The association of genome-wide DNAm with BDR and FeNO has been assessed using regression models, adjusting for age, sex, ancestry, and tissue heterogeneity. Cross-tissue validation was assessed in 50 nasal samples. Differentially methylated regions (DMRs) and enrichment in traits and biological pathways were assessed. A false discovery rate (FDR) < 0.1 and a genome-wide significance threshold of p < 9 × 10 -8 were used to control for false-positive results. The CpG cg12835256 ( PLA2G12A ) was genome-wide associated with FeNO in blood samples (coefficient= -0.015, p = 2.53 × 10 -9 ) and nominally associated in nasal samples (coefficient = -0.015, p = 0.045). Additionally, three CpGs were suggestively associated with BDR (FDR < 0.1). We identified 12 and four DMRs associated with FeNO and BDR (FDR < 0.05), respectively. An enrichment in allergic and inflammatory processes, smoking, and aging was observed. We reported novel associations of DNAm markers associated with BDR and FeNO enriched in asthma-related processes.

There is a clinical need to identify children with poor asthma control as early as possible, to optimize treatment and/or to find therapeutic alternatives. Here, we present the "Systems Pharmacology Approach to Uncontrolled Pediatric Asthma" (SysPharmPediA) study, which aims to establish a pediatric cohort of moderate-to-severe uncontrolled and controlled patients with asthma, to investigate pathophysiological mechanisms underlying uncontrolled moderate-to-severe asthma in children on maintenance treatment, using a multi-omics systems medicine approach. In this multicenter observational case-control study, moderate-to-severe asthmatic children (age; 6-17 years) were included from four European countries (Netherlands, Germany, Spain, and Slovenia). Subjects were classified based on asthma control and number of exacerbations. Demographics, current and past patient/family history, and clinical characteristics were collected. In addition, systems-wide omics layers, including epi(genomics), transcriptomics, microbiome, proteomics, and metabolomics were evaluated from multiple samples. In all, 145 children were included in this cohort, 91 with uncontrolled (median age = 12 years, 43% females) and 54 with controlled asthma (median age = 11.7 years, 37% females). The two groups did not show statistically significant differences in age, sex, and body mass index z-score distribution. Comprehensive information and diverse noninvasive biosampling procedures for various omics analyses will provide the opportunity to delineate underlying pathophysiological mechanisms of moderate-to-severe uncontrolled pediatric asthma. This eventually might reveal novel biomarkers, which could potentially be used for noninvasive personalized diagnostics and/or treatment.

Several dietary components have been shown to influence alcohol metabolism and thereby potentially affect the development of a hangover. From the literature, it is evident that dietary nicotinic acid and zinc play a pivotal role in the oxidation of ethanol into acetaldehyde. The aim of the current study was to associate dietary intake of nicotinic acid and zinc with hangover severity. To this end, data from n = 23 healthy social drinkers who participated in a naturalistic hangover study were analyzed. n = 10 of them reported to be hangover-resistant (the control group), whereas n = 13 reported to have regular hangovers (the hangover-sensitive group). Two 24 h dietary recall records were completed, one for the day of alcohol consumption and another one for an alcohol-free control day. Dietary nutrient intake was averaged and did not significantly differ between hangover-sensitive and hangover-resistant drinkers. For the hangover-sensitive drinkers, partial correlations with overall hangover severity were computed, controlling for estimated blood alcohol concentration. A bootstrapping technique was applied to account for the relatively small sample size. The results showed that dietary intake of nicotinic acid (r PB = -0.521) and zinc (r PB = -0.341) were significantly and negatively associated ( p < 0.002) with overall hangover severity. Dietary zinc intake was also significantly and negatively associated with severity of vomiting (r PB = -0.577, p < 0.002). No significant associations with hangover severity were found for other nutrients, such as fat and fibers. In conclusion, this study suggests that social drinkers who have a higher dietary intake of nicotinic acid and zinc report significantly less severe hangovers. As hangover-resistant and hangover-sensitive drinkers had a similar dietary nutrient intake, the claim of being hangover-resistant must be based on other unknown biopsychosocial factors. These findings should be replicated in a larger sample and include more elaborate food frequency questionnaires or nutrient-specific dietary intake records for zinc and nicotinic acid, and preferably accompanied by nutrient assessments in urine and/or blood., Competing Interests: J.G. is part-time employee of Nutricia Research and received research grants from Nutricia research foundation, Top Institute Pharma, Top Institute Food and Nutrition, GSK, STW, NWO, Friesland Campina, CCC, Raak-Pro, and EU. A.D.K. has received grants/research support from Top Institute Pharma, NWO, Janssen, GSK, Nutricia Research, and Friesland Campina. J.C.V. has received grants/research support from the Dutch Ministry of Infrastructure and the Environment, Janssen, Nutricia, Red Bull, Sequential, and Takeda, and has acted as a consultant for Canadian Beverage Association, Centraal Bureau Drogisterijbedrijven, Clinilabs, Coleman Frost, Danone, Deenox, Eisai, Janssen, Jazz, More Labs, Purdue, Red Bull, Sanofi-Aventis, Sen-Jam Pharmaceutical, Sepracor, Takeda, Toast!, Transcept, Trimbos Institute, Vital Beverages, and ZBiotics. A.S. has held research grants from Abbott Nutrition, Arla Foods, Bayer Healthcare, Cognis, Cyvex, GlaxoSmithKline, Naturex, Nestle, Martek, Masterfoods, Wrigley, and has acted as a consultant/expert advisor to Abbott Nutrition, Barilla, Bayer Healthcare, Danone, Flordis, GlaxoSmithKline Healthcare, Masterfoods, Martek, Novartis, Unilever, and Wrigley.The other authors have not potential conflicts of interest to disclose.

Background: Irritable bowel syndrome (IBS) can have a significant negative impact on quality of life, mood and wellbeing. The aim of this study was to investigate the association between experiencing IBS symptoms and insomnia, and perceived health status., Method: An online survey was conducted among n = 1950 Dutch university students (83.6% women). IBS was assessed with the Birmingham IBS Symptom Questionnaire, quality of life with the WHO-5 wellbeing index, and sleep outcomes with the SLEEP-50 questionnaire. Perceived immune functioning and general health were assessed using 1-item scales., Results: IBS symptom severity was significantly associated with insomnia complaints (r = 0.32, p = 0.0001), sleep quality (r = -0.21, p = 0.0001), sleep onset latency (r = 0.11, p = 0.0001) and the number of nightly awakenings (r = 0.24, p = 0.0001). Total sleep time was not significantly associated with IBS symptom severity. Significant correlations were also found between IBS symptom severity and perceived general health (r = -0.30, p = 0.0001), perceived immune functioning (r= -0.25, p = 0.0001), and quality of life (r = -0.24, p = 0.0001)., Conclusions: Experiencing IBS complaints is associated with reduced perceived immune functioning, a poorer perception of general health, and sleep disturbances. These effects are reflected in a significantly lower reported quality of life in subjects with more IBS and/or sleep complaints.