Derivation of a prototype asthma attack risk scale centred on blood eosinophils and exhaled nitric oxide

Reduction of the risk of asthma attacks is a major goal of current asthma management. We propose to derive a risk scale predicting asthma attacks based on the blood eosinophil count and exhaled nitric oxide. Biomarker-stratified trial-level attack rates were extracted and pooled from the control arms of the Novel START, CAPTAIN, QUEST, Benralizumab Phase 2b, PATHWAY, STRATOS 1-2 and DREAM trials (n=3051). These were used to derive rate ratios and the predicted asthma attack rate for different patient groups. The resultant prototype risk scale shows potential to predict asthma attacks, which may be prevented by anti-inflammatory treatment

Recovery of Breakthrough Asthma Attacks Treated With Oral Steroids while on monoclonal antibody therapy: protocol for a prospective observational study (BOOST)

Background: Asthma attacks are a common and important problem. Someone experiences an asthma attack in the United Kingdom every 10 seconds. Asthma attacks cause coughing, wheezing, breathlessness, and chest tightness and are highly stressful for patients. They result in reduced quality of life, with days lost from work or school. Asthma attacks are treated with oral corticosteroids (OCSs), but these have many short- and long-term side effects. Asthma monoclonal antibodies (mAbs) have revolutionized the treatment of severe asthma by reducing asthma attacks and OCS burden by over 50%, but some people still experience attacks while on mAbs. The MEX study showed that residual asthma attacks are broadly eosinophilic (high fractional exhaled nitric oxide [FeNO]) or noneosinophilic (low FeNO), but it did not measure response to OCS treatment. There is an evidence gap in understanding the clinical and inflammatory responses that occur when using OCSs to treat residual asthma attacks in patients taking asthma mAbs. Objective: The primary objective is to compare the clinical recovery between high-FeNO and low-FeNO attacks after acute treatment with oral prednisolone among people established on long-term asthma mAb treatment. The exploratory objective is to compare the inflammatory response to acute treatment with oral prednisolone between high-FeNO and low-FeNO attacks. Methods: BOOST (Breakthrough Asthma Attacks Treated With Oral Steroids) is a single-center, prospective observational study of 60 adults established on long-term asthma mAb treatment who receive acute treatment with oral prednisolone (usual care) for an asthma attack. The primary outcome will be the proportion of treatment failure (the need to start oral prednisolone or antibiotics or an unscheduled health care visit for asthma, following an attack) at day 28. The secondary outcomes will be the change in forced expiratory volume in 1 second and the change in visual analogue scale symptom score between the stable state, attack, day 7, and day 28 visits. The exploratory outcomes include the changes in sputum, nasal, and blood inflammometry between the stable state, attack, day 7, and day 28 visits. Results: The last asthma attack visit is anticipated to occur in December 2023. Data analysis and publication will take place in 2024. Conclusions: We will test the hypothesis that there is a difference in the rate of recovery of clinical and inflammatory measures between high-FeNO and low-FeNO asthma attacks that occur in patients on mAb therapy. The study data will help power a future randomized placebo-controlled trial of prednisolone treatment for nonsevere attacks in patients treated with asthma mAbs and will provide important information on whether corticosteroid treatment should be FeNO-directed. International Registered Report Identifier (IRRID): DERR1-10.2196/4674

True interindividual variability exists in postprandial appetite responses in healthy men but is not moderated by the FTO genotype

Background: After meal ingestion, a series of coordinated hormone responses occur concomitantly with changes in perceived appetite. It is not known whether interindividual variability in appetite exists in response to a meal. Objectives: This study aimed to 1) assess the reproducibility of appetite responses to a meal; 2) quantify individual differences in responses; and 3) explore any moderating influence of the fat mass and obesity associated (FTO) gene. Methods: Using a replicated crossover design, 18 healthy men (mean ± SD 28.5 ± 9.8 years, 27.0 ± 5.0 kg·m-2 ) recruited according to FTO genotype (9 AA, 9 TT) completed two identical control and two identical standardized meal conditions (5025 kJ) in randomized sequences. Perceived appetite and plasma acylated ghrelin, total peptide YY (PYY), insulin and glucose concentrations were measured before and after interventions as primary outcomes. Interindividual differences were explored using Pearson’s product-moment correlations between the first and second replicate of the control-adjusted meal response. Within-participant covariate-adjusted linear mixed models were used to quantify participant by-condition and genotype-by-condition interactions. Results: The meal suppressed acylated ghrelin and appetite perceptions (standardized effect sizes (ES): 0.18-4.26) and elevated total PYY, insulin and glucose (ES: 1.96-21.60). For all variables, SD of change scores was greater in the meal versus control conditions. Moderate-to-large positive correlations were observed between the two replicates of control-adjusted meal responses for all variables (r=0.44-0.86, P≤0.070). Participant-by-condition interactions were present for all variables (P≤0.056). FTO genotype-by-condition interactions were not significant (P≥0.19) and treatment effect differences between genotype groups were small (ES≤0.27) for all appetite parameters. Conclusions: Reproducibility of postprandial appetite responses is generally good. True interindividual variability is present beyond any random within-subject variation in healthy men but is not moderated by the FTO genotype. These findings highlight the 3 importance of exploring individual differences in appetite for the prevention and/or treatment of obesity. Clinical trial registry number: NCT03771690 (ClinicalTrials.gov)

Gatecliff Shelter

552 p. : ill., maps ; 26 cm.Includes bibliographical references (p. 530-552)

A comparison of fast and slow contraction speeds using electromyography

The purpose of this study was to determine if differences in EMG activity existed between fast and slow contraction speeds during isolated, one-armed biceps curls to muscle failure. Participants performed one set of biceps curls to muscular failure on two separate occasions at different contraction speeds. Constant load equal to 75% of 1RM was used for each test. The dependent variables were integrated EMG (iEMG), percent change in mean frequency, and time to muscular failure. Integrated EMG measurements revealed significantly greater muscle activity for the slow contractions (t = 4.76, p {dollar}\u3c{dollar}.001). The time to muscular failure also showed significant differences having the fast contraction speed achieve muscle failure faster than the slow contraction speed (t = 5.23, p {dollar}\u3c{dollar}.001). The comparison of frequency data failed to reach significance. A significant correlation (r =.514) was determined for iEMG and time to muscular failure. These results suggest that differences exist in iEMG and time to muscle failure between fast and slow contraction speeds