Aeroallergen Sensitization, Serum IgE, and Eosinophilia as Predictors of Response to Omalizumab Therapy during the Fall Season among Children with Persistent Asthma

BACKGROUND: Perennial aeroallergen sensitization is associated with greater asthma morbidity and is required for treatment with omalizumab. OBJECTIVE: To investigate the predictive relationship between the number of aeroallergen sensitizations, total serum IgE, and serum eosinophil count, and response to omalizumab in children and adolescents with asthma treated during the fall season. METHODS: This analysis includes inner-city patients with persistent asthma and recent exacerbations aged 6-20 years comprising the placebo and omalizumab-treated groups in two completed randomized clinical trials, the Inner-City Anti-IgE Therapy for Asthma (ICATA) study and the Preventative Omalizumab or Step-Up Therapy for Fall Exacerbations (PROSE) study. Logistic regression modeled the relationship between greater degrees of markers of allergic inflammation and the primary outcome of fall season asthma exacerbations. RESULTS: The analysis included 761 participants who were 62% male and 59% African American with a median age of 10 years. Fall asthma exacerbations were significantly higher in children with greater numbers of aeroallergen-specific sensitizations in the placebo group (OR 1.33, 95% CI 1.11-1.60, p CONCLUSIONS: In preventing fall season asthma exacerbations, treatment with omalizumab was most beneficial in children with a greater degree of allergic inflammation

After Lisbon: National Parliaments in the European Union

The role of national parliaments in EU matters has become an important subject in the debate over the democratic legitimacy of European Union decision-making. Strengthening parliamentary scrutiny and participation rights at both the domestic and the European level is often seen as an effective measure to address the perceived 'democratic deficit' of the EU - the reason for affording them a prominent place in the newly introduced 'Provisions on Democratic Principles' of the Union (in particular Article 12 TEU). Whether this aim can be met, however, depends crucially on the degree and the manner in which national parliaments actually make use of their institutional rights. This volume therefore aims at providing a comprehensive overview of the activities of national parliaments in the post-Lisbon era. This includes the 'classic' scrutiny of EU legislation, but also parliamentary involvement in EU foreign policy, the use of new parliamentary participation rights of the Lisbon Treaty (Early Warning System), their role regarding the EU's response to the eurozone crisis and the, so far under-researched, role of parliamentary administrators in scrutiny processes. This introduction provides the guiding theoretical framework for the contributions. Based on neo-institutionalist approaches, it discusses institutional capacities and political motivation as the two key explanatory factors in the analysis of parliamentary involvement in EU affairs

Vitamin D3 attenuates Th2 responses to Aspergillus fumigatus mounted by CD4+ T cells from cystic fibrosis patients with allergic bronchopulmonary aspergillosis

Allergic bronchopulmonary aspergillosis (ABPA) is caused by a dominant Th2 immune response to antigens derived from the opportunistic mold Aspergillus, most commonly Aspergillus fumigatus. It occurs in 4%–15% of patients with cystic fibrosis (CF); however, not all patients with CF infected with A. fumigatus develop ABPA. Therefore, we compared cohorts of A. fumigatus–colonized CF patients with and without ABPA to identify factors mediating tolerance versus sensitization. We found that the costimulatory molecule OX40 ligand (OX40L) was critical in driving Th2 responses to A. fumigatus in peripheral CD4+ T cells isolated from patients with ABPA. In contrast, CD4+ T cells from the non-ABPA cohort did not mount enhanced Th2 responses in vitro and contained a higher frequency of TGF-β–expressing regulatory T cells. Heightened Th2 reactivity in the ABPA cohort correlated with lower mean serum vitamin D levels. Further, in vitro addition of 1,25 OH-vitamin D3 substantially reduced DC expression of OX40L and increased DC expression of TGF-β. This in vitro treatment also resulted in increased Treg TGF-β expression and reduced Th2 responses by CD4+ T cells from patients with ABPA. These data provide rationale for a therapeutic trial of vitamin D to prevent or treat ABPA in patients with CF