Alcohol hangover versus dehydration revisited: The effect of drinking water to prevent or alleviate the alcohol hangover.

The alcohol hangover is a combination of negative mental and physical symptoms which can be experienced after a single episode of alcohol consumption, starting when blood alcohol concentration (BAC) approaches zero. A popular theory suggests that dehydration is the primary cause of alcohol hangover and that the consumption of water could alleviate hangover symptoms. Here, the current evidence on the relationship between hangover severity, thirst, and water consumption is summarized. The positive correlations of the amount of water consumed with both hangover severity and thirst suggest that both dehydration and the hangover are co-occurring after-effects of alcohol consumption. While hangovers were typically relatively enduring, dehydration effects were usually mild and short-lasting. Survey data revealed that water consumption during or directly after alcohol consumption had only a modest effect in preventing next-day hangover. Also, the amount of water consumed during hangover was not related to changes of hangover severity and thirst. Thus, water consumption was not effective to alleviate the alcohol hangover. Taken together, these data suggests that alcohol hangover and dehydration are two co-occurring but independent consequences of alcohol consumption.

Comparative Analysis of the Clinical Presentation of Individuals Who Test Positive or Negative for SARS-CoV-2: Results from a Test Street Study.

The common cold, the flu, and the 2019 coronavirus disease (COVID-19) have many symptoms in common. As such, without testing for severe-acute-respiratory-syndrome-related coronavirus 2 (SARS-CoV-2), it is difficult to conclude whether or not one is infected with SARS-CoV-2. The aim of the current study was to compare the presence and severity of COVID-19-related symptoms among those who tested positive or negative for the beta variant of SARS-CoV-2 (B.1.351) and identify the clinical presentation with the greatest likelihood of testing positive for SARS-CoV-2. n = 925 individuals that were tested for SARS-CoV-2 at Dutch mass testing sites (i.e., test streets) were invited to complete a short online survey. The presence and severity of 17 COVID-19-related symptoms were assessed. In addition, mood, health correlates, and quality of life were assessed for the week before the test. Of the sample, n = 88 tested positive and n = 837 tested negative for SARS-CoV-2. Individuals who tested positive for SARS-CoV-2 reported experiencing a significantly greater number, as well as greater overall symptom severity, compared to individuals who tested negative for SARS-CoV-2. A binary logistic regression analysis revealed that increased severity levels of congestion, coughing, shivering, or loss of smell were associated with an increase in the odds of testing positive for SARS-CoV-2, whereas an increase in the severity levels of runny nose, sore throat, or fatigue were associated with an increase in the odds of testing negative for SARS-CoV-2. No significant differences in mood or health correlates were found between those who tested positive or negative for SARS-CoV-2, except for a significantly higher stress score among those who tested negative for SARS-CoV-2. In conclusion, individuals that tested positive for SARS-CoV-2 experienced a significantly greater number and more severe COVID-19-related symptoms compared to those who tested negative for SARS-CoV-2. Experiencing shivering and loss of smell may be the best indicators for increased likelihood of testing positive for SARS-CoV-2.

Alcohol hangover recognized as a separate medical condition in ICD-11: could effective treatments be counterproductive?

Recently, the alcohol hangover has been accepted by the International Classification of Diseases - 11th revision as a separate 'child entity' to alcohol intoxication, a disease. Currently there are no marketed hangover treatments with support for clinical efficacy. Furthermore, diverse perspectives exist among healthcare professionals, policymakers, and alcohol consumers regarding the necessity and desirability of developing such treatments.

Sex and age differences in self-reported immune fitness.

Studies have reported sex and age differences in self-rated health. On average, women rate their health as being poorer compared to men, and older individuals report poorer health than younger individuals. The current study evaluated sex and age differences for self-reported immune fitness, i.e. the capacity of the body to respond to health challenges (such as infections) by activating an appropriate immune response in order to promote health and prevent and resolve disease. Data from different survey studies (N = 8586) were combined for the current analyses. N = 8064 participants (93.3%) completed the single-item scale to assess momentary immune fitness (mean (Standard deviation, SD) age of 32.4 (16.7) years old, range: 18 to 103, 68.0% women) and N = 4263 participants (49.7%) completed the Immune Status Questionnaire (ISQ) to assess past year's immune fitness (mean (SD) age of 40.9 (17.1) years old, range: 18 to 103, 61.1% women). The analyses revealed that women rated their momentary and past year's immune fitness significantly lower than men (p < 0.001). A small but significant decline in momentary immune fitness when aging was found (r = -0.073, p < 0.001). In contrast, past year's immune fitness steadily improved with progressing age (r = 0.295, p < 0.001), and for each age group the difference from the 18-24 years old group was statistically significant (p < 0.001). When using age as covariate, the sex differences in immune fitness remained significant for both momentary immune fitness (p < 0.001) and past year's immune fitness (p < 0.001). In conclusion, women report a poorer momentary and past year's immune fitness than men. The sex effects in immune fitness are robust and seen across all age groups except the elderly. A relative stable momentary immune fitness was found across the age groups. However, past year's immune fitness (assessments with the ISQ) improved with age. This observation may be related to the fact that the studies comprised convenience samples. Therefore, the observed age effects should be interpreted with caution and require further investigation in nationally representative samples.

Absenteeism, Presenteeism, and the Economic Costs of Alcohol Hangover in The Netherlands.

The alcohol hangover is defined as the combination of negative mental and physical symptoms that can be experienced after a single episode of alcohol consumption, starting when the blood alcohol concentration (BAC) approaches zero. Alcohol hangover symptoms such as fatigue, nausea, and headache can negatively affect daily activities, including work performance. The alcohol hangover can therefore be a cause of both absenteeism (not going to work) and presenteeism (going to work while hungover). An online survey among a convenience sample of n = 347 Dutch adults examined the number of days of absenteeism and presenteeism associated with having a hangover as well as the loss of productivity when going to work when hungover during the year 2019. In the Dutch sample, 8.1% of employees reported one or more days of absenteeism due to hangover in 2019, and 33.4% reported one or more days of presenteeism. The analyses revealed that alcohol hangover was associated with 0.2 days of absenteeism and 8.3 days of presenteeism and a productivity loss of 24.9% on days worked with a hangover. The estimated associated costs for the Dutch economy in 2019 of absenteeism (EUR 234,538,460) and presenteeism (EUR 2,423,603,184) total EUR 2,658,141,644. In conclusion, the alcohol hangover is associated with absenteeism, presenteeism, and reduced performance at work while hungover. As such, the annual costs of the alcohol hangover have a significant impact on the Dutch economy. However, these first findings on the economic costs of the alcohol hangover should be considered a rough estimate. They should be verified in a longitudinal study to minimize recall bias, including a nationally representative sample of sufficient sample size.

Towards consistency in dietary pattern scoring: standardising scoring workflows for healthy dietary patterns using 24-h recall and two variations of a food frequency questionnair.

Healthy dietary patterns such as the Mediterranean diet (MeDi), Dietary Approaches to Stop Hypertension (DASH) and the Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) have been evaluated for their potential association with health outcomes. However, the lack of standardisation in scoring methodologies can hinder reproducibility and meaningful cross-study comparisons. Here we provide a reproducible workflow for generating the MeDi, DASH and MIND dietary pattern scores from frequently used dietary assessment tools including the 24-h recall tool and two variations of FFQ. Subjective aspects of the scoring process are highlighted and have led to a recommended reporting checklist. This checklist enables standardised reporting with sufficient detail to enhance the reproducibility and comparability of their outcomes. In addition to these aims, valuable insights in the strengths and limitations of each assessment tool for scoring the MeDi, DASH and MIND diet can be utilised by researchers and clinicians to determine which dietary assessment tool best meets their needs.

Novel paradigms for the gut-brain axis during alcohol withdrawal, withdrawal-associated depression, and craving in patients with alcohol use disorder.

Introduction: Patients with alcohol use disorder (AUD) exhibit symptoms such as alcohol withdrawal, depression, and cravings. The gut-immune response may play a significant role in manifesting these specific symptoms associated with AUD. This study examined the role of gut dysfunction, proinflammatory cytokines, and hormones in characterizing AUD symptoms. Methods: Forty-eight AUD patients [men (n = 34) and women (n = 14)] aged 23-63 years were grouped using the Clinical Institute Withdrawal Assessment of Alcohol Scale (CIWA) as clinically significant (CS-CIWA [score > 10] [n = 22]) and a clinically not-significant group (NCS-CIWA [score ≤ 10] [n = 26]). Clinical data (CIWA, 90-day timeline followback [TLFB90], and lifetime drinking history [LTDH]) and blood samples (for testing proinflammatory cytokines, hormones, and markers of intestinal permeability) were analyzed. A subset of 16 AUD patients was assessed upon admission for their craving tendencies related to drug-seeking behavior using the Penn-Alcohol Craving Score (PACS). Results: CS-CIWA group patients exhibited unique and significantly higher levels of adiponectin and interleukin (IL)-6 compared to NCS-CIWA. In the CS group, there were significant and high effects of association for the withdrawal score with gut-immune markers (lipopolysaccharide [LPS], adiponectin, IL-6, and IL-8) and for withdrawal-associated depression with gut-immune markers (scored using MADRS with LPS, soluble cells of differentiation type 14 [sCD14], IL-6, and IL-8). Craving (assessed by PACS, the Penn-Alcohol Craving Scale) was significantly characterized by what could be described as gut dysregulation (LBP [lipopolysaccharide binding protein] and leptin) and candidate proinflammatory (IL-1ß and TNF-α) markers. Such a pathway model describes the heavy drinking phenotype, HDD90 (heavy drinking days past 90 days), with even higher effects (R2 = 0.955, p = 0.006) in the AUD patients, who had higher ratings for cravings (PACS > 5). Discussion: The interaction of gut dysfunction cytokines involved in both inflammation and mediating activity constitutes a novel pathophysiological gut-brain axis for withdrawal symptoms and withdrawal-associated depression and craving symptoms in AUD. AUD patients with reported cravings show a significant characterization of the gut-brain axis response to heavy drinking. Trial registration: ClinicalTrials.gov, identifier: NCT# 00106106.

Mapping Temperature Heterogeneities during Catalytic CO2 Methanation with Operando Luminescence Thermometry.

Controlling and understanding reaction temperature variations in catalytic processes are crucial for assessing the performance of a catalyst material. Local temperature measurements are challenging, however. Luminescence thermometry is a promising remote-sensing tool, but it is cross-sensitive to the optical properties of a sample and other external parameters. In this work, we measure spatial variations in the local temperature on the micrometer length scale during carbon dioxide (CO2) methanation over a TiO2-supported Ni catalyst and link them to variations in catalytic performance. We extract local temperatures from the temperature-dependent emission of Y2O3:Nd3+ particles, which are mixed with the CO2 methanation catalyst. Scanning, where a near-infrared laser locally excites the emitting Nd3+ ions, produces a temperature map with a micrometer pixel size. We first designed the Y2O3:Nd3+ particles for optimal temperature precision and characterized cross-sensitivity of the measured signal to parameters other than temperature, such as light absorption by the blackened sample due to coke deposition at elevated temperatures. Introducing reaction gases causes a local temperature increase of the catalyst of on average 6-25 K, increasing with the reactor set temperature in the range of 550-640 K. Pixel-to-pixel variations in the temperature increase show a standard deviation of up to 1.5 K, which are attributed to local variations in the catalytic reaction rate. Mapping and understanding such temperature variations are crucial for the optimization of overall catalyst performance on the nano- and macroscopic scale.

The relationship between immune fitness and saliva biomarkers of systemic inflammation.

Purpose: It is vital that Immune fitness, i.e., how well the immune system functions and reacts to challenges, can be reliably be examined. The current study aimed to compare immune fitness with assessments of saliva biomarkers of systemic inflammation. Methods: N = 108 healthy young adults (18-30-year-old students of Utrecht University, the Netherlands) participated in the study. A saliva sample was collected for biomarker assessment (Interleukin (IL)-1ß, IL-6, IL-8, IL-10, immunoglobulin A (IgA), and tumor necrosis factor-alpha (TNF-α), and c-reactive protein (CRP). Additionally, a survey was completed to assess immune fitness, mood, mental resilience, and quality of life. The correlations between the biomarker assessments, immune fitness and mood were determined. Results: No significant correlations between immune fitness and biomarkers of systemic inflammation were found. Significant sex differences in correlations with immune fitness were demonstrated for loneliness (significant only in men) and fatigue (significant only in women). For both sexes, immune fitness correlated significantly with anxiety, mental resilience, and quality of life. Conclusion: No significant correlations were found between immune fitness and saliva biomarkers of systemic inflammation. Immune fitness correlated significantly with anxiety, mental resilience, and quality of life. Sex differences were demonstrated in the relation of immune fitness with loneliness and fatigue. Future research should further investigate factors that may influence the relationship between immune fitness, mood, and biomarkers of systemic inflammation, including underlying psychological mechanisms of possible sex differences.

The efficacy of a combination of naproxen and fexofenadine (SJP - 002) to inhibit the symptoms that are associated with viral upper respiratory tract infection: Four case reports of individuals with common cold.

Key Clinical Message: There is no effective treatment that reduces both the severity and duration of a common cold episode. SJP - 002 (naproxen and fexofenadine) reduced symptom severity by two-third, and the duration of the common cold episode approximately by half. Abstract: The common cold is one of the most frequently experienced immune-related complaints. At present, available treatments have limited efficacy in inhibiting symptoms associated with upper respiratory tract infection, nor do they significantly shorten the duration of common cold episodes. Four case reports are presented of individuals with a common cold. Three of them self-administered the combination of naproxen and fexofenadine (SJP - 002). Results of one individual were compared to her spouse, who did not take SJP - 002 to treat common cold, while two other individuals took SJP - 002 and compared symptom severity with another common cold episode they experienced previously without taking SJP - 002. SJP - 002 reduced the severity of symptoms associated with upper respiratory tract infection by two-third and reduced the duration of the common cold episode approximately by half. In conclusion, SJP - 002 reduced the severity and duration of common cold episodes. These findings warrant further investigation of SJP - 002 in double-blind, placebo-controlled clinical trials.

An evening of alcohol consumption negatively impacts next-day immune fitness in both hangover-sensitive drinkers and hangover-resistant drinkers.

BACKGROUND: Survey research found poorer baseline immune fitness for self-reported hangover-sensitive drinkers compared to hangover-resistant drinkers. However, up to now a limited number of clinical studies revealed mixed results regarding the relationship between the concentrations of biomarkers of systemic inflammation in blood or saliva with hangover severity, and could not differentiate between hangover-sensitive drinkers and hangover-resistant drinkers. The aim of this study was to assess immune fitness and saliva biomarkers of systemic inflammation at multiple timepoints following an alcohol day and alcohol-free control day. METHODS: The study had a semi-naturalistic design. In the evening before the test days, participants were not supervised. They could drink ad libitum drinking on the alcohol test day and refrained from drinking alcohol on the control day. Activities and behaviors on the alcohol and control day were reported the follow morning. On both test days, from 09:30 to 15:30, hourly assessments of immune fitness (single-item scale) and overall hangover severity (single-item scale) were made and saliva samples were collected for biomarker assessments. RESULTS: N = 14 hangover-resistant drinkers and n = 15 hangover-sensitive drinkers participated in the study. The amount of alcohol consumed on the alcohol day did not significantly differ between the hangover-resistant group (mean (SD) of 13.5 (7.9) alcoholic drinks) and the hangover-sensitive group (mean (SD) of 12.4 (4.4) alcoholic drinks). All hangover-sensitive drinkers reported having a hangover following the alcohol day (overall hangover severity score 6.1 (on a 0-10 scale) at 09:30, gradually decreasing to 3.3 at 15:30), whereas the hangover-resistant drinkers reported no hangover. On the control day, immune fitness of the hangover-sensitive group was significantly poorer than the hangover-resistant group. On the alcohol day, both groups showed a significant reduction in immune fitness. The effect was evident throughout the day, but significantly more pronounced in the hangover-sensitive group than the hangover-resistant group. No significant differences between the groups were found at any time point on the two test days for saliva concentrations of Interleukin (IL)-1ß, IL-6, IL-8, and tumor necrosis factor (TNF)-α. CONCLUSIONS: Whereas hangover-sensitive drinkers reported a hangover following an alcohol day and hangover-resistant drinkers did not, both groups reported significantly reduced immune fitness throughout the day. However, the reduction in immune fitness among hangover-sensitive drinkers was significantly more pronounced in comparison to the hangover-resistant group.

Immune Fitness, Migraine, and Headache Complaints in Individuals with Self-Reported Impaired Wound Healing.

Background: Having chronic wounds and impaired wound healing are associated with psychological distress. The current study aims to evaluate migraine and headache complaints in young adults with self-reported impaired wound healing. Methods: A survey was conducted among N=1935 young adults (83.6% women), 18-30 years old, living in the Netherlands. Wound healing status was verified, immune fitness was assessed using a single-item rating scale, and ID Migraine was completed. In addition, several questions were answered on past year's headache experiences (including frequency, quantity, type, location, and severity). Results: In both the control group (p < 0.001) and the IWH group (p = 0.002) immune fitness was significantly lower among those that reported headaches compared to those that reported no headaches. Individuals with self-reported impaired wound healing (IWH) scored significantly higher on the ID Migraine scale, and individuals of the IWH group scored significantly more often positive for migraine (ie, an ID Migraine score ≥2). They reported a younger age of onset of experiencing headaches, and significantly more often reported having a beating or pounding headache than the control group. Compared to the control group, the IWH group reported being significantly more limited in their daily activities compared to the control group. Conclusion: Headaches and migraines are more frequently reported by individuals with self-reported impaired wound healing, and their reported immune fitness is significantly poorer compared to healthy controls. These headache and migraine complaints significantly limit them in their daily activities.

Predictors of Hangover Frequency and Severity: The Impact of Alcohol Consumption, Mental Resilience, Personality, Lifestyle, Coping and Mood.

Mental resilience is the ability to bounce back from daily life stressors such as divorce or losing a job. Extensive research has demonstrated a negative relationship between mental resilience and alcohol consumption. That is, both the quantity and frequency of alcohol consumption are greater in individuals with lower levels of mental resilience. There has, however, been little scientific attention paid to the relationship between mental resilience and alcohol hangover severity. The objective of this study was to evaluate psychological factors that may impact the frequency and severity of alcohol hangovers, including alcohol intake itself, mental resilience, personality, baseline mood, lifestyle, and coping mechanisms. An online survey was conducted among Dutch adults (N = 153) who had a hangover after their heaviest drinking occasion in the period before the start of the COVID-19 pandemic (15 January to 14 March 2020). Questions were asked about their alcohol consumption and hangover severity on their heaviest drinking occasion. Mental resilience was assessed with the Brief Mental Resilience scale, personality with the Eysenck Personality Questionnaire-Revised Short Scale (EPQ-RSS), mood via single item assessments, and lifestyle and coping with the modified Fantastic Lifestyle Checklist. The partial correlation, corrected for estimated peak blood alcohol concentration (BAC), between mental resilience and hangover severity was not significant (r = 0.010, p = 0.848). Furthermore, no significant correlations were found between hangover severity or frequency and personality and baseline mood. For lifestyle and coping factors, a negative correlation was found between the use of tobacco and toxins (i.e., drugs, medicines, caffeine) and the frequency of experiencing hangovers. Regression analysis revealed that hangover severity after the heaviest drinking occasion (31.2%) was the best predictor of hangover frequency, and that subjective intoxication on the heaviest drinking occasion (38.4%) was the best predictor of next-day hangover severity. Mood, mental resilience, and personality were not relevant predictors of hangover frequency and severity. In conclusion, mental resilience, personality, and baseline mood do not predict hangover frequency and severity.

The Impact of COVID-19 Lockdowns in Germany on Mood, Attention Control, Immune Fitness, and Quality of Life of Young Adults with Self-Reported Impaired Wound Healing.

BACKGROUND: Previous studies in Dutch young adults revealed that individuals with self-reported impaired wound healing reported poorer mood, increased inattention and impulsivity, poorer quality of life, and poorer immune fitness compared to healthy controls. Another study revealed that the negative impact of lockdowns during the 2019 coronavirus disease (COVID-19) pandemic was significantly more profound among the impaired wound healing group than the control group. The purpose of the current study was to replicate and extend these findings among young adults living in Germany. METHODS: A retrospective, cross-sectional survey was conducted among N = 317 young adults living in Germany, 18-35 years old. They were allocated to the IWH group (N = 66) or the control group (N-251). Participants completed the Attention Control Scale, and mood, quality of life, and immune fitness were assessed with single-item ratings. All assessments were made for (1) the period before the COVID-19 pandemic, (2) the first lockdown period, March-May 2020, (3) the first no-lockdown period, summer 2020, (4) the second lockdown, November 2020 to May 2021, and (5) the second no-lockdown period, summer 2021. RESULTS: The impaired wound healing group reported significantly poorer mood, quality of life, and immune fitness. The effects were evident before the pandemic. The impaired wound healing group scored significantly poorer on attention focusing, but no significant differences between the groups were found for attention shifting. During the pandemic, negative lockdown effects (i.e., further aggravation of mood and immune fitness and lower quality of life) were evident in both groups but significantly more profound in the impaired wound healing group. No differences between the groups were found for the no-lockdown periods. CONCLUSION: Individuals with self-reported impaired wound healing have significantly poorer mood, attention focusing, and immune fitness and report a poorer quality of life than healthy controls. The impact of COVID-19 lockdowns was significantly more profound in the impaired wound-healing group.

Test-retest reliability of single-item assessments of immune fitness, mood, and quality of life.

The use of single-item assessments is increasingly important and popular, as these enable quick real-time assessments in clinical practice or research. In this study we investigated the test-retest reliability of single-item assessments of mood ("stress", "anxiety", "depression", "fatigue", "loneliness", "being active", "optimism", and "happiness"), quality of life, and immune fitness in N = 108 participants. The analysis revealed high test-retest correlations between the single-item assessments (r = 0.67 to 0.90), moderate to excellent intraclass correlations (r = 0.672 to 0.889), and the Bland-Altman analysis revealed agreement between all test-retest assessments, except for depression. Taken together, it can be concluded that the single-item assessments of mood, quality and immune fitness have a good test-retest reliability. This strengthens the rationale for using these single item assessments.

Emotion Regulation and Mood during the COVID-19 Pandemic.

The 2019 coronavirus disease (COVID-19) pandemic has had a significant negative impact on health, mood, and well-being [...].

Depression, Anxiety, and Stress among Hangover-Sensitive and Hangover-Resistant Drinkers.

This study investigated potential differences in baseline (i.e., non-hangover-related) levels of depression, anxiety, and stress between individuals who are sensitive to and those resistant to hangovers after consuming alcohol. Participants included 5111 university students from the Netherlands and the U.K., including 3205 hangover-sensitive and 1906 hangover-resistant drinkers. All participants completed surveys on their demographics, alcohol consumption, and hangover susceptibility (whether they experienced a hangover in the past 12 months), as well as their baseline levels of depression, anxiety, and stress on the DASS-21 scale. The results showed that hangover-sensitive drinkers had significantly higher levels of anxiety and stress, but not depression, compared to hangover-resistant drinkers. However, the observed differences between the two groups were small, with a magnitude of less than 1 out of 42 points on the DASS-21 anxiety and stress subscales, and are thus unlikely to be clinically meaningful.

Wound drainage after arthroplasty and prediction of acute prosthetic joint infection: prospective data from a multicentre cohort study using a telemonitoring app.

Background: Differentiation between uncomplicated and complicated postoperative wound drainage after arthroplasty is crucial to prevent unnecessary reoperation. Prospective data about the duration and amount of postoperative wound drainage in patients with and without prosthetic joint infection (PJI) are currently absent. Methods: A multicentre cohort study was conducted to assess the duration and amount of wound drainage in patients after arthroplasty. During 30 postoperative days after arthroplasty, patients recorded their wound status in a previously developed wound care app and graded the amount of wound drainage on a 5-point scale. Data about PJI in the follow-up period were extracted from the patient files. Results: Of the 1019 included patients, 16 patients (1.6 %) developed a PJI. Minor wound drainage decreased from the first to the fourth postoperative week from 50 % to 3 %. Both moderate to severe wound drainage in the third week and newly developed wound drainage in the second week after a week without drainage were strongly associated with PJI (odds ratio (OR) 103.23, 95 % confidence interval (CI) 26.08 to 408.57, OR 80.71, 95 % CI 9.12 to 714.52, respectively). The positive predictive value (PPV) for PJI was 83 % for moderate to heavy wound drainage in the third week. Conclusion: Moderate to heavy wound drainage and persistent wound drainage were strongly associated with PJI. The PPV of wound drainage for PJI was high for moderate to heavy drainage in the third week but was low for drainage in the first week. Therefore, additional parameters are needed to guide the decision to reoperate on patients for suspected acute PJI.

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.