IgA+ memory B-cells are significantly increased in patients with asthma and small airway dysfunction.

BACKGROUND: Comprehensive studies investigated the role of T-cells in asthma which led to personalised treatment options targeting severe eosinophilic asthma. However, little is known about the contribution of B-cells to this chronic inflammatory disease. In this study we investigated the contribution of various B-cell populations to specific clinical features in asthma. METHODS: In the All Age Asthma Cohort (ALLIANCE), a subgroup of 154 adult asthma patients and 28 healthy controls were included for B-cell characterisation by flow cytometry. Questionnaires, lung function measurements, blood differential counts and allergy testing of participants were analysed together with comprehensive data on B-cells using association studies and multivariate linear models. RESULTS: Patients with severe asthma showed decreased immature B-cell populations while memory B-cells were significantly increased compared with both mild-moderate asthma patients and healthy controls. Furthermore, increased frequencies of IgA+ memory B-cells were associated with impaired lung function and specifically with parameters indicative for augmented resistance in the peripheral airways. Accordingly, asthma patients with small airway dysfunction (SAD) defined by impulse oscillometry showed increased frequencies of IgA+ memory B-cells, particularly in patients with mild-moderate asthma. Additionally, IgA+ memory B-cells significantly correlated with clinical features of SAD such as exacerbations. CONCLUSIONS: With this study we demonstrate for the first time a significant association of increased IgA+ memory B-cells with asthma and SAD, pointing towards future options for B-cell-directed strategies in preventing and treating asthma.

Multi-centre randomised trial of invasive and less invasive surfactant delivery methods showed similar spirometry results at 5-9 years of age.

AIM: We explored whether subnormal forced expiratory volume within 1 s (FEV1 ) at 5-9 years of age was lower in children born preterm who received less invasive surfactant administration (LISA) rather than surfactant via an endotracheal tube. METHODS: The multi-centre, randomised Nonintubated Surfactant Application trial enrolled 211 preterm infants born at 23-26 weeks of gestation from 13 level III neonatal intensive care units from April 2009 to March 2012. They received surfactant via LISA (n = 107) or after conventional endotracheal intubation (n = 104). The follow-up assessments were carried out by a single team blinded to the group assignments. The main outcome was FEV1 < 80% of predicted values. RESULTS: Spirometry was successful in 102/121 children. The other children died or were lost to follow-up. Median FEV1 was 93% (interquartile range 80%-113%) of predicted values in the LISA group and 86% (interquartile range 77-102%) in the control group (p = 0.685). Rates of FEV1 < 80% were 11/57 (19%) and 15/45 (33%), respectively, which was an absolute risk reduction of 14% (95% confidence interval -3.1% to 31.2%, p = 0.235). There were no differences in other outcome measures. CONCLUSION: The proportion of children aged 5-9 years with subnormal FEV1 was not significantly different between the groups.

Regression Analyses and Their Particularities in Observational Studies.

BACKGROUND: Regression analysis is a standard method in medical research. It is often not clear, however, how the individual components of regression models are to be understood and interpreted. In this article, we provide an overview of this type of analysis and discuss its special features when used in observational studies. METHODS: Based on a selective literature review, the individual components of a regression model for differently scaled outcome variables (metric: linear regression; binary: logistic regression; time to event: Cox regression; count variable: Poisson or negative binomial regression) are explained, and their interpretation is illustrated with respect to a study on multiple sclerosis. The prerequisites for the use of each of these models, their applications, and their limitations are described in detail. RESULTS: Regression analyses are used to quantify the relation between several variables and the outcome variable. In randomized clinical trials, this flexible statistical analysis method is usually lean and prespecified. In observational studies, where there is a need to control for potential confounders, researchers with knowledge of the topic in question must collaborate with experts in statistical modeling to ensure high model quality and avoid errors. Causal diagrams are an increasingly important basis for evaluation. They should be constructed in collaboration and should differentiate between confounders, mediators, and colliders. CONCLUSION: Researchers need a basic understanding of regression models so that these models will be well defined and their findings will be fully reported and correctly interpreted.

The "Shiny and Thick High Heel Sign" : A novel radiologic sign for detecting intracranial dural arteriovenous fistulas with time-of-flight magnetic resonance angiography.

PURPOSE: Together with the foramen ovale, the middle meningeal artery (MMA) looks like a high heel shoe print on axial time-of-flight magnetic resonance angiography (TOF-MRA) images, with the MMA resembling the heel. Cranial dural arteriovenous fistulas (DAVF) are often fed by the MMA, which can lead to an increase of signal intensity and diameter of this vessel, resulting in a more "shiny" and "thick" high heel print appearance than on the contralateral side. We describe this finding as a novel radiologic sign and provide cut-off values for the ratios of MMA signal intensities and diameters for predicting the presence of a DAVF. METHODS: A total of 84 TOF-MRA examinations of 44 patients with DAVFs (40 with unilateral MMA feeders, 4 with bilateral feeders) and of 40 patients without DAVFs were included. Diameters and signal intensities of both MMAs were measured by two raters and evaluated using receiver operating characteristic analysis. RESULTS: The diameters of feeding and non-feeding MMAs differed significantly, as did the ratios of signal intensities and of diameters of DAVF and control patients (P < 0.0001). Cut-off values were 1.25 for average signal intensity ratio (shiny high heel sign) and 1.21 for diameter ratio (thick high heel sign). The combination of the "shiny" and the "thick" high heel sign resulted in the highest sensitivity (92.5%) and positive predictive value (95%). CONCLUSION: The described sign seems promising for the detection of DAVFs with noncontrast-enhanced MRI. The TOF-MRA source images should be reviewed with special attention to the MMA.

A Digital Health Application Allowing a Personalized Low-Glycemic Nutrition for the Prophylaxis of Migraine: Proof-of-Concept Data from a Retrospective Cohort Study.

BACKGROUND: Migraine is a headache disorder with the highest socioeconomic burden. The aim of this study was to deliver the first proof-of-concept data of the potential role of an individual low-glycemic diet provided by a novel digital health application in the prophylaxis of migraine. METHODS: We analyzed data from a retrospective survey of individuals who participated in a digital nutrition program that provides dietary recommendations based on the individual analysis of continuous glucose measurement from an up to 14-day test phase. A total of 84 individuals completed the retrospective digital survey. The endpoints were changes in the number of migraine days, average duration of attacks, average pain severity, frequency of intake of pain medication, absenteeism, and presenteeism before and after program participation. RESULTS: The intraindividual comparisons of the endpoints before and after program participation revealed decreases in migraine frequency and other patient-relevant migraine parameters. Moreover, patients with a baseline migraine frequency of two and more migraine days per month and adherence to the dietary recommendations (n = 40) showed a mean reduction in migraine days by 33% with a 50%-responder rate of 38%. CONCLUSIONS: The data provides emerging evidence that an individualized low-glycemic diet based on continuous glucose measurement could be a promising approach for a diet-based, non-pharmacological migraine prophylaxis. However, future research is required to confirm the implied effectiveness.