Clinical risk factors for severe asthma attacks have been identified, but their incremental prognostic values are unclear. Additionally, the incremental contribution of type 2 inflammation, a common, treatable process, is undetermined. We aimed to quantify the prognostic value of baseline characteristics and type 2 inflammatory biomarkers, specifically blood eosinophil count and fractional exhaled nitric oxide (FeNO), to predict asthma attacks. In this systematic review and meta-analysis of randomised controlled trials (RCTs), Oxford Asthma Attack Risk Scale 2 (ORACLE2), we searched MEDLINE from Jan 1, 1993, to April 1, 2021, for trials investigating fixed treatment regimen effects on asthma attack rates for at least 6 months with baseline blood eosinophil count and FeNO. Eligible participants were aged 12 years or older with asthma (any severity) who had been randomly assigned to the control group of an RCT. Relevant trials were manually retrieved and reviewed by two independent reviewers (SC and IDP). Disagreements were discussed with five reviewers. Individual patient data (IPD) for meta-analysis were requested from study authors. We investigated the rate of severe asthma attacks (≥3 days of systemic corticosteroids) for at least 6 months and prognostic effects of baseline blood eosinophil count and FeNO in control group participants. Rate ratios (RRs) with 95% CIs were derived for annualised asthma attack rates from negative binomial models adjusted for key variables, including blood eosinophil count and FeNO, and interactions between these type 2 inflammatory biomarkers were explored. Certainty of evidence was assessed using GRADE. The heterogeneity of the included studies and potential for ecological bias were quantified by the concordance statistic (C-statistic). This study was registered with PROSPERO, CRD42021245337. We identified 976 potentially eligible studies. After automated screening, we manually reviewed 219 full-text articles. Of these, 19 publications comprising 23 RCTs were eligible. 6513 participants (4140 [64%] female; 2370 [36%] male; three missing) spanning 22 RCTs were included for data analysis. 5972 (92%) of 6513 patients had moderate-to-severe asthma. 4615 asthma attacks occurred during 5482 person-years of follow-up (annualised rate 0·84 per person-year). Higher blood eosinophil count or FeNO was linked to higher asthma attack risk (per 10-fold increase, RR 1·48 [95% CI 1·30-1·68] for blood eosinophil count and 1·44 [1·26-1·65] for FeNO; high-certainty evidence). Other prognostic factors were attack history (yes vs no, RR 1·94 [1·61-2·32]); disease severity (severe vs moderate, RR 1·57 [1·22-2·03]); FEV₁ percentage predicted (FEV₁%; per 10% decrease, RR 1·11 [1·08-1·15]); and 5-item Asthma Control Questionnaire score (ACQ-5; per 0·5 increase, RR 1·10 [1·07-1·13]). High blood eosinophil count and FeNO combined were associated with greater risk than either prognostic factor separately. Bronchodilator reversibility was associated with lower risk of severe asthma attacks (per 10% increase, RR 0·93 [0·90-0·96]), with the reduction observed primarily between 0% and 25%. Regarding heterogeneity of the included studies, the C-statistic ranged from 0·58 to 0·95, indicating major differences in patient and disease characteristics between studies. In the univariable meta-analysis per trial, we found substantial heterogeneity in associations between studies, with I² statistics ranging from 0·56 to 0·97. Blood eosinophil count, FeNO, asthma attack history, disease severity, low lung function (low FEV₁%), and symptoms (ACQ-5 score) are key predictors of asthma attacks. Conversely, we found that moderate bronchodilator reversibility was associated with reduced risk. These findings from high-quality multinational RCTs support incorporation of blood eosinophils and FeNO into clinical risk stratification for targeted risk reduction. More individualised clinical decision-making models should be explored. National Institute of Health and Care Research Oxford Biomedical Research Centre; Association pulmonaire du Québec; Fonds de recherche du Québec-Santé; Québec Air-Intersectorialité-Respiratoire-Son network; Stichting Astma Bestrijding; Leiden University Fund; and Academy of Medical Sciences.

Oxidative stress has been proposed as a key contributor to lifestyle- and age-related diseases. Because free radicals play an important role in various processes such as immune responses and cellular signaling, the body possesses an arsenal of different enzymatic and non-enzymatic antioxidant defense mechanisms. Oxidative stress is, among others, the result of an imbalance between the production of various reactive oxygen species (ROS) and antioxidant defense mechanisms including vitamin E (α-tocopherol) as a non-enzymatic antioxidant. Dietary vitamins, such as vitamin C and E, can also be taken in as supplements. It has been postulated that increasing antioxidant levels through supplementation may delay and/or ameliorate outcomes of lifestyle- and age-related diseases that have been linked to oxidative stress. Although supported by many animal experiments and observational studies, randomized clinical trials in humans have failed to demonstrate any clinical benefit from antioxidant supplementation. Nevertheless, possible explanations for this discrepancy remain underreported. This review aims to provide an overview of recent developments and novel research techniques used to clarify the existing controversy on the benefits of antioxidant supplementation in health and disease, focusing on α-tocopherol as antioxidant. Based on the currently available literature, we propose that examining the difference between antioxidant activity and capacity, by considering the catabolism of antioxidants, will provide crucial knowledge on the preventative and therapeutical use of antioxidant supplementation in oxidative stress-related diseases.

Remote teaching and assessment are essential for current education. During online examination, online proctoring is often used as a surveillance tool. Little is known about student perceptions on online proctoring. Using an online questionnaire, we found that medical students worry most about unjustified invalidation of their exam due to unstable internet connection, background noise or webcam issues, and privacy issues. It is important to be aware of these worries as they may influence test results.

The antioxidant vitamin E (α-tocopherol, α-TOH) protects lipids from oxidation by reactive oxygen species. We hypothesized that lifestyle factors associate with vitamin E metabolism marked by urinary α-tocopheronolactone hydroquinone (α-TLHQ) and α-carboxymethyl-hydroxychroman (α-CEHC levels), as potential reflection of lipid oxidation. We conducted a cross-sectional study in the Netherlands Epidemiology of Obesity Study. Serum α-TOH, and urinary α-TLHQ and α-CEHC were quantified by liquid chromatography coupled with tandem mass spectrometry. Information on the lifestyle factors (sleep, physical activity (PA), smoking and alcohol) were collected through questionnaires. Multivariable linear regression analyses were performed to assess the associations between the lifestyle factors and α-TOH measures. A total of 530 participants (46% men) were included with mean (SD) age of 56 (6) years. Of the examined lifestyle factors, only poor sleep was associated with a higher serum α-TOH (mean difference: 4% (95% CI: 1, 7%)). Current smoking was associated with higher urinary α-CEHC (32%: (14%, 53%)), with evidence of a dose–response relationship with smoking intensity (low pack years, 24% (2, 52%); high pack years, 55% (25, 93%)). Moderate physical activity was associated with a lower α-TLHQ relative to α-CEHC (−17%: (−26, −6%), compared with low PA). Only specific lifestyle factors associate with vitamin E metabolism. Examining serum α-TOH does not provide complete insight in vitamin E antioxidant capacity.

While obesity increases the risk of developing cardiometabolic diseases (CMDs), these associations seem to attenuate with increasing age, albeit studied poorly. The present study aimed to investigate the associations between adiposity and CMDs in sex-specific groups of chronological age and leukocyte telomere length (LTL) as a measure of biological age. We investigated the associations between BMI, a body shape index, waist-to-hip ratio (adjusted for BMI) and total body fat, and incident coronary artery disease (CAD), type 2 diabetes (T2D) and ischemic stroke (IS) in 413,017 European-ancestry participants of the UK Biobank without CMD at baseline. We assessed the change in the associations between adiposity and CMD over strata of increasing chronological age or decreasing LTL. Participants (56% women) had a median (IQR) age of 57.0 (50.0–63.0) years. The median follow-up time was 12 years. People with higher BMI had a higher risk of incident CAD (HR 1.14 (95% confidence interval [CI] 1.13, 1.16)), T2D (HR 1.70 (95% CI 1.68, 1.72)) and IS (HR 1.09 (95% CI 1.06, 1.12)). In groups based on chronological age and LTL, adiposity measures were associated with higher risk of CAD and T2D in both men and women, but these associations attenuated with increasing chronological age (P_interactions < 0.001), but not with decreasing LTL (P_interaction men = 0.85; P_interaction women = 0.27). Increased (abdominal) adiposity was associated with higher risk of incident CMDs, which attenuated with increasing chronological age but not with decreasing LTL. Future research may validate these findings using different measures of biological age.