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BACKGROUND The pathology of pediatric severe therapy-resistant asthma (STRA) is little understood. OBJECTIVES We hypothesized that STRA in children is characterized by airway eosinophilia and mast cell inflammation and is driven by the T(H)2 cytokines IL-4, IL-5, and IL-13. METHODS Sixty-nine children (mean age, 11.8 years; interquartile range, 5.6-17.3(More)
Patients with severe refractory asthma pose a major healthcare problem. Over the last decade it has become increasingly clear that, for the development of new targeted therapies, there is an urgent need for further characterisation and classification of these patients. The Unbiased Biomarkers for the Prediction of Respiratory Disease Outcomes (U-BIOPRED)(More)
RATIONALE Structural alterations to airway smooth muscle (ASM) are a feature of asthma and cystic fibrosis (CF) in adults. OBJECTIVES We investigated whether increase in ASM mass is already present in children with chronic inflammatory lung disease. METHODS Fiberoptic bronchoscopy was performed in 78 children (median age [IQR], 11.3 [8.5-13.8] yr): 24(More)
RATIONALE Airway inflammation is characteristic of asthma. Distal inflammation may be particularly important. OBJECTIVE To calculate alveolar nitric oxide (NO) concentration (C(alv)) and bronchial flux NO (J(NO)) in children. METHODS We measured C(alv) and J(NO) from the fractional exhaled NO (FeNO(50)) measured at multiple exhalation flow rates in 132(More)
PURPOSE OF REVIEW The management of children with difficult asthma requires a systematic approach. These children are prescribed high doses of inhaled or oral corticosteroids and a balance must be struck between therapeutic efficacy and side effects. It is important to ensure the diagnosis is correct and that the reasons for poor control in a given child(More)
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(More)
BACKGROUND Two distinct, stable inflammatory phenotypes have been described in adults with asthma: eosinophilic and non-eosinophilic. Treatment strategies based on these phenotypes have been successful. This study evaluated sputum cytology in children with asthma to classify sputum inflammatory phenotypes and to assess their stability over time. METHODS(More)
BACKGROUND Previous studies in adults with asthma incorporating the control of sputum eosinophils into management strategies have shown significant reductions in exacerbations. A study was undertaken to investigate whether this strategy would be successful in children with severe asthma. METHODS 55 children (7-17 years) with severe asthma were randomised(More)
BACKGROUND The mechanism underlying severe asthma with fungal sensitization (SAFS) is unknown. IL-33 is important in fungus-induced asthma exacerbations, but its role in fungal sensitization is unexplored. OBJECTIVE We sought to determine whether fungal sensitization in children with severe therapy-resistant asthma is mediated by IL-33. METHODS(More)