Epigenome-Wide Association Studies of the Fractional Exhaled Nitric Oxide and Bronchodilator Drug Response in Moderate-to-Severe Pediatric Asthma.

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.

Perceived Immune Fitness, Individual Strength and Hangover Severity.

Various factors may contribute to alcohol hangover severity. The purpose of the current investigation was to evaluate the possible impact of alcohol consumption patterns, perceived immune status, and baseline fatigue on hangover severity. A survey was completed by a convenience sample of N = 199 Dutch students who reported on their latest past month's heavy drinking occasion, including subjective intoxication (perceived drunkenness) and next-day hangover severity, which were rated on single-item scales ranging from 0 (absent) to 10 (extreme). In addition, perceived (momentary) immune fitness was assessed, and the Checklist Individual Strength (CIS) was completed to assess baseline fatigue. The analysis revealed that instead of the amount of alcohol consumed or estimated blood alcohol concentration, it appeared that subjective intoxication (i.e., level of drunkenness) was the most important determinant of alcohol hangover severity. Especially in men, albeit modest, it was perceived that immune fitness also significantly contributed to the level of hangover severity experienced.