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Notes: Background In humans the prevalence of asthma is higher among females than among males after puberty. The reason for this phenomenon is not clear.Objective We tested the hypothesis that female mice are more susceptible to the development of allergic asthma than male mice and studied allergic immune responses in the lung.Methods We compared allergic airway inflammation, i.e. methacholine (MCh) responsiveness, serum IgE, and cytokines, and the number of the different leucocytes in lungs of male and female BALB/c mice, twice-sensitized to ovalbumin (OVA) and subsequently challenged with OVA (OVA-mice) or phosphate-buffered saline (PBS-mice) aerosols on days 24–26, 30, and 31.Results OVA challenge significantly increased MCh responsiveness, numbers of eosinophils, CD4+ T cells, CD4+/CD25+ T cells, B cells, and levels of Thelper (Th)2 cytokines, total, and OVA-specific IgE. There was, however, also an effect of gender, with female mice responding to OVA challenges with higher numbers of eosinophils, CD4+ T cells, B cells, and levels of IL-4, IL-13, IFN-γ, total, and OVA-specific IgE than male mice. In contrast, female PBS-mice had significantly lower percentages of regulatory CD4+/CD25+ T cells than males (females 4.2±0.2% vs. males 5.3±0.1% of CD4+ T cells, P〈0.05).Conclusion Female mice develop a more pronounced type of allergic airway inflammation than male mice after OVA challenge. The reduced percentage of regulatory T cells in the lungs of female PBS-mice may indicate that the level of these cells in the lung during the sensitization phase is important for the development and/or progression of an allergic immune response after multiple OVA challenges.

Notes: Background There is a large variability in clinical response to corticosteroid treatment in patients with asthma. Several markers of inflammation like eosinophils and eosinophil cationic protein (ECP), as well as exhaled nitric oxide (NO), are good candidates to predict clinical response.Aim We wanted to determine whether we could actually predict a favourable response to inhaled corticosteroids in individual patients.Methods One hundred and twenty patients with unstable asthma were treated with either prednisolone 30 mg/day, fluticasone propionate 1000 µg/day b.i.d. or fluticasone propionate 250 µg/day b.i.d., both via Diskhaler. They were treated during 2 weeks, in a double-blind, parallel group, double dummy design. We measured eosinophils and ECP in blood and sputum, and exhaled nitric oxide as inflammatory parameters before and after 2 weeks in order to predict the changes in forced expiratory volume in 1 s (FEV1), provocative concentration of methacholine causing a 20% fall in FEV1 (PC20 Mch), and asthma quality of life (QOL). Secondly, to test whether these results were applicable in clinical practice we determined the individual prediction of corticosteroid response.Results We found that changes in FEV1, PC20 Mch and QOL with corticosteroids were predominantly predicted by their respective baseline value and to a smaller extent by eosinophils in blood or sputum. ECP, measured in blood or sputum, was certainly not better than eosinophils in predicting clinical response to corticosteroids. Smoking status was an additional predictor for change in FEV1, but not for change in PC20 Mch or QOL. Prediction of a good clinical response was poor. For instance, high sputum eosinophils (≥ 3%) correctly predicted an improvement in PC20 Mch in only 65% of the patients.Conclusion Our findings show that baseline values of the clinical parameters used as outcome parameters are the major predictors of clinical response to corticosteroids. Eosinophil percentage in blood or sputum adds to this, whereas ECP provides no additional information. Correct prediction of clinical response in an individual patient, however, remains poor with our currently used clinical and inflammatory parameters.

Notes: Introduction Bronchial hyper-responsiveness is usually measured with direct stimuli such as methacholine (MCh) or histamine. Adenosine 5′-monophosphate (AMP), which acts indirectly via the secondary release of mediators, is another stimulus to measure bronchial hyper-responsiveness.Aim To investigate whether provocation with inhaled AMP itself initiates an inflammatory response resulting in an influx of eosinophils into the airway lumen.Methods We have included 21 non-smoking atopic asthmatic subjects (mean FEV1 101% predicted, mean age 34 years). Each subject performed three sputum inductions on different days, at least seven days apart: one without previous provocation, one hour after PC20 methacholine, and one hour after PC20 AMP.Results After provocation with AMP, but not methacholine, the percentage of sputum eosinophils increased significantly (from 1.9±0.5% to 4.5±1% (P〈0.01) and 1.9±0.5% (P=0.89)). No changes in the percentages of neutrophils, lymphocytes, macrophages, or bronchial epithelial cells were found.Conclusion A provocation test with AMP leads to an increased percentage of sputum eosinophils. This observation cannot be explained by a non-specific response of the airways to a vigorous bronchoconstriction, since methacholine had no effect on inflammatory cells.