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Asthmatic Response (asthmatic + response)
Selected AbstractsAllergen provocation increases TH2-cytokines and FOXP3 expression in the asthmatic lungALLERGY, Issue 3 2010S. Thunberg To cite this article: Thunberg S, Gafvelin G, Nord M, Grönneberg R, Grunewald J, Eklund A, van Hage M. Allergen provocation increases TH2-cytokines and FOXP3 expression in the asthmatic lung. Allergy 2010; 65: 311,318. Abstract Background:, Allergic asthma is caused by allergen-specific IgE and T-helper cell (Th) type 2 responses towards airborne allergens. The objective of this study was to investigate local and systemic regulatory mechanisms in the early asthmatic response to bronchial allergen provocation. Methods:, Birch pollen-allergic patients with mild asthma (n = 13) and healthy nonallergic controls (n = 14) were subjected to bronchoalveolar lavage (BAL) and blood sampling. On patients BAL was performed twice: without preceding provocation (,before samples') and 24 h after bronchial provocation with birch pollen allergen. Lymphocytes in BAL and peripheral blood mononuclear cells (PBMCs) were phenotyped by multi-colour flow cytometry and cytokines measured by cytometric bead array. Proliferation and secreted cytokines were analysed in allergen-stimulated PBMCs, CD25+ depleted PBMCs and PBMCs with IL-10 neutralizing antibodies. Results:, The numbers of CD69+ and FOXP3+ lymphocytes were higher in BAL after compared with before allergen provocation in asthmatic patients. Moreover, allergen provocation increased expression of FOXP3 in CD4+CD25bright cells. The cytokine profile in BAL fluid from asthmatics revealed higher levels of IL-5, compared with the controls, and an increase in IL-5, IL-6, IL-9 and IL-10 after allergen provocation. Pollen allergen stimulated PBMC cultures from asthmatic patients produced elevated levels of IL-5 and IL-13 compared with the controls, which were not affected by depletion of CD25+ cells or IL-10 neutralization. Conclusion:, Despite an increase in CD4+CD25bright cells expressing high levels of FOXP3 in response to bronchial allergen provocation, asthmatic patients exhibit enhanced levels of Th2 cytokines in the lung, which may indicate an inability among infiltrating cells to suppress Th2 responses. [source] Sputum eosinophilia: an early marker of bronchial response to occupational agentsALLERGY, Issue 5 2009O. Vandenplas Background:, False-negative responses to specific inhalation challenge (SIC) with occupational agents may occur. We explored whether assessing changes in sputum cell counts would help improve the identification of bronchial reactivity to occupational agents during SICs. Methods:, The predictive value of the changes in sputum cell counts after a negative FEV1 response to a first challenge exposure to an occupational agent was determined using the changes in airway calibre observed during repeated challenges as the ,gold standard'. The study included 68 subjects investigated for work-related asthma in a tertiary centre. After a control day, the subjects were challenged with the suspected occupational agent(s) for up to 2 h. All subjects who did not show an asthmatic reaction were re-challenged on the following day. Additional challenges were proposed to those who demonstrated a , 2% increase in sputum eosinophils or an increase in nonspecific bronchial hyperresponsiveness to histamine after the second challenge day. Results:, Six of the 35 subjects without changes in FEV1 on the first challenge developed an asthmatic reaction on subsequent challenges. ROC analysis revealed that a >3% increase in sputum eosinophils at the end of the first challenge day was the most accurate parameter for predicting the development of an asthmatic response on subsequent challenges with a sensitivity of 67% and a specificity of 97%. Conclusions:, An increase in sputum eosinophils is an early marker of specific bronchial reactivity to occupational agents, which may help to identify subjects who will develop an asthmatic reaction only after repeated exposure. [source] IgE , a marker of late asthmatic response?CLINICAL & EXPERIMENTAL ALLERGY, Issue 2 2001K. S. Babu First page of article [source] Plasma protein profiles in early asthmatic responses to inhalation allergen challengeALLERGY, Issue 1 2009T. Rhim Although mediators, such as lipids, cytokines, and chemokines, are related to the appearance of an IPR, there has been no reliable indicator to predict conditions for the appearance of an IPR. In this study, we adopted a proteomic approach to investigate the pathogenesis at the level of the plasma proteins and to develop plasma markers to predict the appearance of an IPR following an inhalation challenge with Dermatophagoides pteronyssinus (D.p.). Sixteen mild asthmatics were recruited. Plasma was obtained before challenge and when a decline in forced expiratory volume in 1 s (FEV1) values greater than 20% from the phosphate-buffered saline value was achieved during D.p. allergen challenge (positive responders), or at 60 min after the highest concentration of D.p. allergen was inhaled (negative responders). After comparing normalized volumes of the spots in the two groups, differentially expressed spots were identified using intra-gel digestion and mass spectrometric analysis. Before D.p. antigen challenge, four spots of gamma fibrinogen and its isoforms were significantly decreased and two spots of complement C3 fragments were significantly increased in the positive responders compared to the negative responders. After D.p. antigen challenge, complement C3 fragment was persistently higher, while gamma fibrinogen was lower in the positive responders than in the negative responders. A validation study using Western blotting showed that gamma fibrinogen expression in the IPR-positive asthmatics was significantly decreased compared to the average of the IPR-negative asthmatic control group. These results indicate that alterations in the complement cascade and fibrinogen may predispose patients to the appearance of an immediate response to D.p. allergen challenge and may provide plasma markers to predict the appearance of an IPR. [source] Eosinophils in bronchial mucosa of asthmatics after allergen challenge: effect of anti-IgE treatmentALLERGY, Issue 1 2009E. L. J. Van Rensen Background:, Anti-IgE, omalizumab, inhibits the allergen response in patients with asthma. This has not been directly related to changes in inflammatory conditions. We hypothesized that anti-IgE exerts its effects by reducing airway inflammation. To that end, the effect of anti-IgE on allergen-induced inflammation in bronchial biopsies in 25 patients with asthma was investigated in a randomized, double-blind, placebo-controlled study. Methods:, Allergen challenge followed by a bronchoscopy at 24 h was performed at baseline and after 12 weeks of treatment with anti-IgE or placebo. Provocative concentration that causes a 20% fall in forced expiratory volume in 1 s (PC20) methacholine and induced sputum was performed at baseline, 8 and 12 weeks of treatment. Changes in the early and late responses to allergen, PC20, inflammatory cells in biopsies and sputum were assessed. Results:, Both the early and late asthmatic responses were suppressed to 15.3% and 4.7% following anti-IgE treatment as compared with placebo (P < 0.002). This was paralleled by a decrease in eosinophil counts in sputum (4,0.5%) and postallergen biopsies (15,2 cells/0.1 mm2) (P < 0.03). Furthermore, biopsy IgE+ cells were significantly reduced between both the groups, whereas high-affinity IgE receptor and CD4+ cells were decreased within the anti-IgE group. There were no significant differences for PC20 methacholine. Conclusion:, The response to inhaled allergen in asthma is diminished by anti-IgE, which in bronchial mucosa is paralleled by a reduction in eosinophils and a decline in IgE-bearing cells postallergen without changing PC20 methacholine. This suggests that the benefits of anti-IgE in asthma may be explained by a decrease in eosinophilic inflammation and IgE-bearing cells. [source] | ||||||||||