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. @ERSpublications Severe asthma results in more airway inflammation, worse symptoms and lower lung function, despite increased therapy http://ow.ly/QznR3

Clustering based on clinicophysiologic parameters yielded 4 stable and reproducible clusters that associate with different pathobiological pathways.

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An increased prevalence of asthma in cross-country skiers has been reported previously. This study was conducted in order to evaluate the prevalence of asthma among young, elite cross-country skiers in Trøndelag, Norway and Jämtland, Sweden. These two regions in central Scandinavia have different climates during the winter season, with a coastal type in Trøndelag while Jämtland is characterized by a colder, drier, inland type of climate. The study population consisted of 171 skiers (118 from Norway, 53 from Sweden). The investigation included an asthma questionnaire, spirometry and methacholine provocation testing. The prevalence of self-reported asthma-related symptoms was 46% in Norway and 51% in Sweden. The prevalence of bronchial hyper-responsiveness (BHR) was significantly different between the two regions. In Norway, 14% of the skiers were hyper-responsive to methacholine compared to 43% in Sweden (P < 0.001). Moreover, the estimated prevalence of clinically diagnosed asthma was 12% in Norway and 42% in Sweden (P < 0.001). The self-reported frequency of respiratory allergy was higher in Sweden (32%) than in Norway (11%). However, on an individual basis, self-reported allergy did not predict occurrence of asthma or BHR. In conclusion, there is a high prevalence of BHR and asthma among young, elite cross-country skiers in central Scandinavia, especially in Sweden. Cross-country skiing may be a risk factor for the development of asthma. Longitudinal studies of cross-country skiers, and studies to acquire further knowledge of the mechanisms involved in the development of asthma are indicated.

Background -The prevalence of asthma and the use of asthma drugs is increasing worldwide. Studies of the incidence of asthma are few but are of interest in finding factors associated with onset of the disease. A study was performed to estimate the incidence of asthma and its relation to sex and to tobacco smoking between the ages of 16 and 19 years, and to compare the incidence of asthma with the proportion of individuals receiving a prescription ofan asthma drug for the first time during one year. Methods -A questionnaire was sent in 1990 to all 3627 individuals born in 1974 living in the county of Jamtland and Gast-

Bronchial hyperresponsiveness to methacholine with asthma-like symptoms ("ski asthma") is frequent in elite cross-country skiers.To further the understanding of "ski asthma", 10 nonasthmatic, nonatopic controls and 30 adolescent elite skiers were investigated by bronchoscopy and bronchoalveolar lavage (BAL). Nine skiers were atopic without allergy symptoms.Compared with controls, the macroscopic inflammatory index in the proximal airways in skiers was three-fold greater (median (interquartile range) 3.0 (2.0±5.0) versus 1.0 (0.8±2.3), p=0.008). In the BAL fluid, skiers had significantly greater total cell (p<0.05) and percentage lymphocyte (p<0.01) and mast cell counts (p<0.05). Neutrophil and eosinophil counts were not significantly different and eosinophil cationic protein was not detected. Tumour necrosis factor-a and myeloperoxidase were detected in 12 (40%) and six (20%) skiers, respectively. In skiers with ski asthma, the inflammatory index was greater than in nonasthmatic skiers. Lymphocyte subtypes and activation markers, and concentration of albumin, fibronectin and hyaluronan were not different from those in controls.Cross-country skiers have a minor to moderate degree of macroscopic inflammation in the proximal airways at bronchoscopy and a bronchoalveolar lavage fluid profile which differs in several respects from healthy controls. Skiers with ski asthma tend to show even higher degrees of bronchial inflammation. Eur Respir J 1999; 13: 626±632.

Observation of bronchus-associated lymphoid tissue (BALT) in whole lung specimens from healthy nonsmoking adults has questioned the hypothesis that BALT is not constitutively present in healthy adult human lungs. In our study, we investigated endobronchial biopsies of the second- and third-generation carinae from 44 cross-country ski athletes and 12 healthy control subjects, all nonsmoking young adults. The skiers had a prevalence of respiratory allergy (18%), asthma-like symptoms (59%), beta2 agonist medication (25%), and methacholine bronchial hyperresponsiveness (79%). Biopsy sections were stained by immunohistochemical and hematoxylin-eosin-saffran methods. Lymphoid aggregates of more than 50 cells were identified in 28 (64%) skiers and three (25%) control subjects (p = 0.02). They were small in comparison to those found in rabbits and rats, contained T and B lymphocytes and macrophages, and were seen more frequently in skiers using beta2 agonists (p = 0.04) and with bronchial hyperresponsiveness to methacholine (p = 0.053). The frequency of these aggregates was not significantly different at the two carinal levels (p = 0.6). The aggregates were not associated with a history of respiratory allergy or asthma-like symptoms. These aggregates share some resemblance with what is usually defined as BALT. However, their exact nature and function await further clarification.

U-BIOPRED cohort n=91 epithelial brushings or biopsies IL-17 High Clinical phenotype Nasal polyps Smoking Antibiotic use Epithelial Gene Expression Profile Clinical phenotype FeNO Exacerbations Gene expression shared with psoriasis IDO1 IL1B DEFB4B S100A8, S100A9 PI3 CXCL3, CXCL8 CXCL10, CCL20 Gene signature SERPINB2 POSTN CLCA1 IL-13 High T cell infiltration Neutrophilia Eosinophilia IL-17-high asthma with features of a psoriasis immunophenotype From a the Respiratory,