Clinical and inflammatory characteristics of the European U-BIOPRED adult severe asthma cohort.

U-BIOPRED is a European Union consortium of 20 academic institutions, 11 pharmaceutical companies and six patient organisations with the objective of improving the understanding of asthma disease mechanisms using a systems biology approach.This cross-sectional assessment of adults with severe asthma, mild/moderate asthma and healthy controls from 11 European countries consisted of analyses of patient-reported outcomes, lung function, blood and airway inflammatory measurements.Patients with severe asthma (nonsmokers, n=311; smokers/ex-smokers, n=110) had more symptoms and exacerbations compared to patients with mild/moderate disease (n=88) (2.5 exacerbations versus 0.4 in the preceding 12 months; p<0.001), with worse quality of life, and higher levels of anxiety and depression. They also had a higher incidence of nasal polyps and gastro-oesophageal reflux with lower lung function. Sputum eosinophil count was higher in severe asthma compared to mild/moderate asthma (median count 2.99% versus 1.05%; p=0.004) despite treatment with higher doses of inhaled and/or oral corticosteroids.Consistent with other severe asthma cohorts, U-BIOPRED is characterised by poor symptom control, increased comorbidity and airway inflammation, despite high levels of treatment. It is well suited to identify asthma phenotypes using the array of "omic" datasets that are at the core of this systems medicine approach.

Explaining differences in the metabolic cost and efficiency of treadmill locomotion in children.

The metabolic cost of locomotion at any given speed, when expressed per kilogram of body mass, is greater for children than for older individuals. Incomplete explanations for the age-related difference motivated this study, which used a multidisciplinary method to examine metabolic, kinematic and electromyographic data from three maturational groups of children. Thirty children aged 7-8 (n = 10), 10-12 (n = 10) and 15-16 (n = 10) years completed 4 min bouts of submaximal treadmill exercise at six speeds--two walking and four running--assigned in random order. Metabolic (net VO2), kinematic (total body mechanical power, energy transfer rates, stride rate) and electromyographic (co-contraction of agonist and antagonist muscles in thigh and leg segments) data were collected. Multiple regression analysis was performed with net VO2 or efficiency as the dependent variable and mechanical power, thigh and leg co-contraction, stride rate and age as independent variables. It was possible to explain up to 77% of the age-related variance in net VO2 and 62% of the variation in efficiency using combinations of these variables. Age was the best single predictor of both VO2 and efficiency. Co-contraction, possibly used to enhance joint stability, was an important component of the observed age-related differences, although mechanical power was not. Additional variance might be explained as specific growth-related factors affecting the metabolic cost of locomotion are identified, as mechanical work models improve, and as methods are developed to measure the effects of stored elastic energy and the metabolic cost of isometric muscle actions.