We have systematically investigated the capacity of highly purified human peripheral CD8+ T cells to produce interleukin (IL)-4 and interferon (IFN)-γ when triggered by different stimuli. CD8+ T cells were isolated from peripheral blood by positive selection to > 99% purity and stimulated with one of three different stimuli: phytohaemagglutinin (PHA) and IL-2, phorbol myristate acetate (PMA) and ionomycin, and plate-bound anti CD3 and PMA. On their own, ionomycin and IL-2 failed to stimulate significant CD8+ T cell proliferation while PHA, plate-bound anti-CD3 and PMA induced weak proliferation. A combination of PHA and IL-2, PMA and ionomycin, or plate-bound anti-CD3 and PMA all induced vigorous CD8+ T cell proliferation. IFN-γ was produced following all three stimuli, but was greatest from cells cultured with PMA and ionomycin. However, IL-4 secretion was only detected in cell cultures stimulated with PMA and ionomycin. These results indicate that, with sufficient stimulation, human CD8+ T cells have the potential to produce Th2 as well as Th1 cytokines.

function (FEV1, FEF25-75, total airway resistance at 5Hz: R5) and on salbutamol FEV1 recovery post histamine challenge. Comparisons were made between genotypes comprising one or two copies of Arg (i.e. ArgArg or ArgGly n = 15, FEV1 = 91.1%, FEF25-75 = 58.3%) vs. no copies of Arg (i.e. GlyGly n = 10, FEV1 = 94.1% FEF25-75 = 60.0%). Results Data are shown in table as change from baseline (i.e. pre vs. post propranolol as means and SEM) within each genotype. Within the Arg genotype there were significant effects of propranolol on FEV1, FEF25-75 and R5 as well as significant blunting of salbutamol response, while in the Gly genotype only salbutamol response was significant. However when comparing the Arg vs. Gly genotypes there were no significant differences for any of the outcomes. Conclusion Propranolol produces significant effects on pulmonary function and salbutamol response in the Arg genotype, although there were no significant differences between Arg and Gly genotypes. -2013-204457.344 Introduction and Objectives It is increasingly recognised that small airway dysfunction is associated with suboptimal asthma control. We have previously reported that b2-adrenoreceptor polymorphism at position 16 (i.e. Arg/Gly) is not related to FEV 1 or airway hyper-responsiveness in persistent asthmatics.

Introduction Therapeutic options for children with severe asthma are limited. Clinical studies support the use of the antiIgE antibody, omalizumab, in children with severe atopic asthma. However, children included in these studies had less severe disease than those in whom omalizumab is currently recommended. Little is known about the clinical efficacy of omalizumab in children with severe therapy resistant asthma (STRA). Objectives To determine the short-term (16 weeks) and longterm (beyond 16 weeks) efficacy of omalizumab, and predictors of a successful therapeutic response in children with STRA in a clinical setting. Methods This was an observational, prospective study of children with STRA who were commenced on omalizumab. Spirometry, bronchodilator reversibility (BDR), exhaled nitric oxide (FE NO ), asthma control test (ACT), mini asthma-related quality of life questionnaire (AQLQ), severe exacerbations (requiring a course of oral corticosteroids (OCS) for ≥3 days) and number of unscheduled healthcare visits (UHCV) and hospital admissions were recorded before and every 4 weeks after commencing treatment. Every 16 weeks, patients underwent a more thorough assessment to determine if the treatment should be continued. Results 33 children (22 male) aged 5-16 years were commenced on omalizumab. At 16 weeks there were significant improvements in mini-AQLQ; ACT; FE NO ; maintenance OCS dose; severe exacerbations and UHCVs. 20/33 (60.6%) children continued omalizumab beyond the initial 16 weeks (up to 192 weeks). Compared to those who discontinued, at baseline these children had higher mini-AQLQ (4.28 vs. 3.05) and ACT (11 vs. 8), were younger (11 vs. 13 years) and were more likely to have been admitted to hospital (57.9% vs. 0%) and have had a severe exacerbation (95% vs. 50%) in the 16 weeks before starting omalizumab. Maximal reduction in number of exacerbations and hospital admissions was evident at 32 weeks; this was maintained for up to 144 weeks (Figure 1). Conclusion This is the first longitudinal study demonstrating long-term clinical efficacy of omalizumab as add-on therapy in children with STRA. Omalizumab was most effective in those with an exacerbation-prone phenotype at baseline, highlighting the importance of thorough patient characterisation when considering this treatment option.