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Asthmatic Subjects (asthmatic + subject)
Selected AbstractsDysregulation of the stress response in asthmatic childrenALLERGY, Issue 1 2009K. N. Priftis The stress system co-ordinates the adaptive responses of the organism to stressors of any kind. Inappropriate responsiveness may account for increased susceptibility to a variety of disorders, including asthma. Accumulated evidence from animal models suggests that exogenously applied stress enhances airway reactivity and increases allergen-induced airway inflammation. This is in agreement with the clinical observation that stressful life events increase the risk of a new asthma attack. Activation of the hypothalamic,pituitary,adrenal (HPA) axis by specific cytokines increases the release of cortisol, which in turn feeds back and suppresses the immune reaction. Data from animal models suggest that inability to increase glucocorticoid production in response to stress is associated with increased airway inflammation with mechanical dysfunction of the lungs. Recently, a growing body of evidence shows that asthmatic subjects who are not treated with inhaled corticosteroids (ICS) are likely to have an attenuated activity and/or responsiveness of their HPA axis. In line with this concept, most asthmatic children demonstrate improved HPA axis responsiveness on conventional doses of ICS, as their airway inflammation subsides. Few patients may experience further deterioration of adrenal function, a phenomenon which may be genetically determined. [source] Predictive value of allergy and pulmonary function tests for the diagnosis of asthma in elite athletesALLERGY, Issue 10 2007M. Bonini Background:, Asthma is frequently found in athletes, often associated with rhinitis and allergy. Aim:, To study the predictive value of allergy and pulmonary function tests for the diagnosis of asthma in athletes. Subjects and methods:, Ninety-eight national preOlympic athletes underwent an accurate medical examination including a validated questionnaire for asthma and rhinitis, spirometric recordings and skin prick testing with a panel of the most frequent inhalant allergens. Bronchodilator and/or exercise challenge were also performed in asthmatic subjects. Results:, Clinical asthma was present in 20.4% of athletes, rhinitis in 35.3% (in 21.4% of cases alone and in 13.9% associated with asthma). Positive prick tests were recorded in 44.4% of athletes (in 60.5% of asthmatics, in 95.2% of rhinitics and in 21.0% of nonasthmatic , nonrhinitic subjects). Mean spirometric values and distribution of abnormal values were not different among asthmatics, rhinitics and nonasthmatics , nonrhinitic patients. Skin-tests positivity was not related to the abnormal spirometric data found in individual cases. Provocation tests with bronchodilators or exercise did not appear sensitive enough to diagnose mild forms of asthma in subjects with normal basal spirometric values. Conclusions:, Allergy testing and spirometry should be performed routinely in athletes because of the high prevalence of allergy, rhinitis and asthma in this population. However, the predictive value of these tests and of the bronchial provocation tests performed in this study seems too low to document mild or subclinical asthma in athletes. [source] Exhaled nitric oxide in asthmatic and non-asthmatic children: Influence of type of allergen sensitization and exposure to tobacco smokePEDIATRIC ALLERGY AND IMMUNOLOGY, Issue 5 2001Mario Barreto Asthmatic bronchial inflammation is associated with increased nitric oxide concentrations in exhaled air (eNO). Recent data suggest that this effect arises from atopy. Our aim in this study was to find out whether atopy and sensitization to particular allergens influences eNO levels. A total of 213 subjects (41 asthmatics and 172 controls) (96 boys and 117 girls, 7.3,14 years of age) were studied. Parents completed a questionnaire that sought information on their children's respiratory symptoms and exposure to tobacco smoke. Subjects underwent skin-prick tests for the following common allergens: Dermatophagoides pteronyssinus (Dpt), cat fur, Aspergillus fumigatus, Alternaria tenuis, mixed grass, mixed tree pollen, Parietaria officinalis, egg, and cow's milk. eNO was collected in 1-l mylar bags (exhaled pressure 10 cmH2O, flow 58 ml/s) and analyzed by using chemiluminescence. Atopic and non-atopic children without a history of chronic respiratory symptoms had a similar geometric mean eNO (atopics, n = 28, 11.2 p.p.b.; non-atopics, n = 96, 10.0 p.p.b.; mean ratio 1.1, 95% confidence interval [CI]: 0.7,1.6). Conversely, atopic asthmatic subjects had significantly higher eNO values than non-atopic asthmatic subjects (atopics, n = 25, 24.8 p.p.b.; non-atopics, n = 16, 11.4 p.p.b.; mean ratio 2.2, 95% CI: 1.2,3.9, p=,0.000). In children with rhinitis alone (n = 15) and those with lower respiratory symptoms other than asthma (n = 33), eNO increased slightly, but not significantly, with atopy. eNO levels correlated significantly with Dpt wheal size (r = 0.51) as well with the wheal size for cat, mixed grass, and Parietaria officinalis (r = 0.30,0.29), and with the sum of all wheals (r = 0.47) (p=,0.000). Subjects sensitized only for Dpt (but not those subjects sensitized only for grass pollen or other allergens) showed significantly higher eNO levels than non-atopic subjects (16.4 p.p.b. vs. 10.2 p.p.b., mean ratio 1.6, 95% CI: 1.1,2.3, p=,0.002). In asthmatic subjects, Dpt sensitization markedly increased eNO levels (Dpt- sensitized subjects: 28.0 p.p.b.; Dpt- unsensitized subjects: 12.2 p.p.b.; mean ratio 2.3, 95% CI: 1.5,3.5, p=,0.000). Non-asthmatic Dpt- sensitized subjects also had significantly higher eNO values than non-asthmatic, non- Dpt -sensitized subjects (14.2 p.p.b. vs. 10.1 p.p.b.; mean ratio 1.4, 95% CI: 1.1,1.9, p=,0.008). No difference was found between eNO levels in asthmatic subjects and control subjects exposed or unexposed to tobacco smoke. In conclusion, eNO concentrations are high in atopic asthmatic children and particularly high in atopic asthmatics who are sensitized to house-dust mite allergen. [source] Effects of inhaled fluticasone propionate on CTLA-4-positive CD4+CD25+ cells in induced sputum in mild asthmaticsRESPIROLOGY, Issue 7 2008Tomotaka KAWAYAMA Background and objective: Cytotoxic T-lymphocyte antigen 4 (CTLA-4) signalling of regulatory T cells regulates mucosal lymphocyte tolerance and differentiation, and may therefore have a beneficial effect in allergic diseases such as asthma. The aim of this study was to evaluate the effects of fluticasone propionate (FP) on CD4+CD25+ T cell co-expression of CTLA-4 in the sputum of mild asthmatic subjects. Methods: Eleven mild, stable asthmatic subjects completed a double-blind, randomized, cross-over, placebo-controlled study to compare the effects of 14 days 200 µg twice daily FP and placebo. Before and after treatment, airway hyperresponsiveness was measured, and sputum was induced for measurements of CTLA-4+CD4+CD25+ cells, eosinophils and levels of IL-10, IL-13 and transforming growth factor (TGF)-, Results: FP treatment increased co-expression of CTLA-4 on sputum CD4+CD25+ cells from a mean (SEM) of 7.9% (1.8) to 12.7% (3.3) after 14 days treatment (P < 0.05) compared with placebo. FP treatment also significantly increased IL-10 levels, reduced per cent sputum eosinophils, and reduced airway hyperresponsiveness (P < 0.05). There was a significant negative correlation between the change in airway hyperresponsiveness and per cent sputum eosinophils (P < 0.01), but no correlation with changes in CTLA-4+CD4+CD25+ cells (P > 0.05). There was no change in the levels of sputum IL-13 or TGF-, Conclusions: The percentage of airway CTLA-4+CD4+CD25+ cells increased after FP treatment, coincident with improvements in airway inflammation and hyperresponsiveness. Whether improved asthma assessments are related to the increase in CTLA-4+CD4+CD25+ cells and thus improved regulation of T-cell tolerance and differentiation will require a larger sample size to determine. The normalization of CTLA-4+CD4+CD25+ cells in asthma may contribute to the management of this disease. [source] Influence of alpha-adrenoceptor blockade on antigen- and propranolol-induced bronchoconstriction in guinea-pigs in vivoAUTONOMIC & AUTACOID PHARMACOLOGY, Issue 1 2000Y. Ishiura 1 Beta-adrenoceptor antagonists, such as propranolol, can provoke severe bronchoconstriction only in asthmatic subjects. Recently, we developed a guinea-pig model of propranolol-induced bronchoconstriction (PIB) and the purpose of this study was to investigate the role of alpha-adrenergic nerve pathways in this reaction. 2 Phentolamine administered after an antigen challenge did not inhibit PIB; however, its administration before the antigen challenge significantly inhibited the antigen-induced bronchoconstriction and also bronchoconstriction induced by methacholine inhalation. 3 We conclude that the alpha-adrenergic nerve system is not involved in the development of PIB following allergic reaction in our guinea-pig model. [source] Induction of glucocorticoid receptor-, expression in epithelial cells of asthmatic airways by T-helper type 17 cytokinesCLINICAL & EXPERIMENTAL ALLERGY, Issue 9 2010A. Vazquez-Tello Summary Background Corticosteroid insensitivity in asthmatics is associated with an increased expression of glucocorticoid receptor-, (GR-,) in many cell types. T-helper type 17 (Th17) cytokine (IL-17A and F) expressions increase in mild and in difficult-to-treat asthma. We hypothesize that IL-17A and F cytokines alone or in combination, induce the expression of GR-, in bronchial epithelial cells. Objectives To confirm the expression of the GR-, and IL-17 cytokines in the airways of normal subjects and mild asthmatics and to examine the effect of cytokines IL-17A and F on the expression of GR-, in bronchial epithelial cells obtained from normal subjects and asthmatic patients. Methods The expression of IL-17A and F, GR-, and GR-, was analysed in bronchial biopsies from mild asthmatics and normal subjects by Q-RT-PCR. Immunohistochemistry for IL-17 and GR-, was performed in bronchial biopsies from normal and asthmatic subjects. The expression of IL-6 in response to IL-17A and F and dexamethasone was determined by Q-RT-PCR using primary airway epithelial cells from normal and asthmatic subjects. Results We detected significantly higher levels of IL-17A mRNA expression in the bronchial biopsies from mild asthmatics, compared with normal. GR-, expression was significantly lower in the biopsies from asthmatics compared with controls. The expression of IL-17F and GR-, in biopsies from asthmatics was not significantly different from that of controls. Using primary epithelial cells isolated from normal subjects and asthmatics, we found an increased expression of GR-, in response to IL-17A and F in the cells from asthmatics (P0.05). This effect was only partially significant in the normal cells. Dexamethasone significantly decreased the IL-17-induced IL-6 expression in cells from normal individuals but not in those from asthmatics (P0.05). Conclusion Evidence of an increased GR-, expression in epithelial cells following IL-17 stimulation suggests a possible role for Th17-associated cytokines in the mechanism of steroid hypo-responsiveness in asthmatic subjects. Cite this as: A. Vazquez-Tello, A. Semlali, J. Chakir, J. G. Martin, D. Y. Leung, D. H. Eidelman and Q. Hamid, Clinical & Experimental Allergy, 2010 (40) 1312,1322. [source] Modulation of the epithelial inflammatory response to rhinovirus in an atopic environmentCLINICAL & EXPERIMENTAL ALLERGY, Issue 3 2008M. Xatzipsalti Summary Background Immune responses to rhinovirus (RV) as well as direct effects of RV on respiratory epithelium may contribute to the induction of asthma exacerbations. Objective To evaluate the effect of the environment resulting from an atopic immune response on RV-induced epithelial inflammation, replication and cytotoxicity. Methods Peripheral blood mononuclear cells (PBMC) from atopic asthmatic subjects and matched controls (12 pairs) were isolated and stimulated by RVs. Human bronchial epithelial (BEAS-2B) cells were infected with RV in the presence of conditioned media from RV-stimulated PBMC cultures. IL-6, IL-8, RANTES and TGF-,1 levels were measured by ELISA, RV-induced cytotoxicity by a colorimetric method and RV titres on Ohio-HeLa cells. Results RV-induced epithelial production of IL-6, IL-8 and RANTES was significantly lower, while TGF-,1 was higher when cells were exposed to conditioned media from atopic asthmatic subjects compared with those from normal controls. Exposure to the ,atopic' environment also resulted in elevated RV titres and increased RV-induced cytotoxicity. Conclusions Under the influence of an atopic environment, the epithelial inflammatory response to RV is down-regulated, associated with increased viral proliferation and augmented cell damage, while TGF is up-regulated. These changes may help explain the propensity of atopic asthmatic individuals to develop lower airway symptoms after respiratory infections and indicate a mechanism through which viral infections may promote airway remodelling. [source] Effects of inhaled ciclesonide on circulating T-helper type 1/T-helper type 2 cells in atopic asthmatics after allergen challengeCLINICAL & EXPERIMENTAL ALLERGY, Issue 11 2006T. Kawayama Summary Background The predominance of T-helper type 2 (Th2) lymphocytes is thought to underlie the pathogenesis of asthma. Allergen inhalation challenge in atopic asthmatic subjects is associated with decreased interferon-, (IFN-,) positive CD4+ and CD8+ lymphocytes in peripheral blood and induced sputum. Objective This study examined the effects of an inhaled corticosteroid on these previously described allergen-induced changes in circulating Th1 and Th2 lymphocytes. Methods Subjects were randomized to 7 days of placebo, 40 or 80 ,g ciclesonide in a crossover study. Airway responses and peripheral blood were measured before and after treatment, and 24 h after allergen challenge. Results Ciclesonide 40 and 80 ,g significantly attenuated the late response and sputum eosinophils at 8 h post-allergen (P<0.05). Circulating IFN-, positive CD4+ lymphocytes decreased after allergen challenge with placebo (P<0.05), and this was inhibited by 40 ,g ciclesonide treatment (P<0.05). There was no effect of allergen inhalation or ciclesonide on IL-4-positive CD4+ lymphocytes or IFN-, and IL-4-positive CD8high lymphocytes. The allergen-induced change of IFN-,/IL-4 ratio on CD4+ cells correlated with the allergen-induced change of peripheral blood eosinophils. Conclusions The results of this study suggest that attenuation of allergen-induced airway responses by ciclesonide may be mediated through regulation of IFN-,-positive CD4+ cells. [source] Increased expression of collagen receptors: ,1,1 and ,2,1 integrins on blood eosinophils in bronchial asthmaCLINICAL & EXPERIMENTAL ALLERGY, Issue 9 2006S. Bazan-Socha Summary Background Eosinophils are one of the major effector cells in bronchial asthma. Their infiltration of airways correlates with the asthma severity. Recruitment and activation of eosinophils are partially mediated by integrins ,4,1 and ,4,7. Collagens type I and IV constitute important components of extracellular matrix and vascular basement membrane, respectively. Therefore, collagen-binding integrins (,1,1 and ,2,1) may also play a role in eosinophil lung infiltration. Objective To evaluate the possible presence of ,1,1 and ,2,1 integrins on peripheral blood eosinophils from asthmatic subjects. Methods Collagen receptors were studied on eosinophils separated by immunomagnetic CD16-negative method from healthy donors (n=13) and patients with moderate persistent atopic bronchial asthma (n=15). Surface receptor identification was performed by flow cytometry and cell adhesion assay. Results Eosinophils isolated from the patients showed increased expression of both ,1,1 and ,2,1 integrins as compared with healthy controls. Moreover, adhesive function of eosinophils to collagen type IV was inhibited by snake venom disintegrins: viperistatin and obtustatin. These disintegrins contain KTS active motif and are specific inhibitors of ,1,1 integrin. Conclusion We demonstrated for the first time that collagen receptors: ,1,1 and ,2,1 integrins are overexpressed on the surface of peripheral blood eosinophils of asthmatic subjects. Further studies may reveal potential application of KTS-disintegrins or their structural analogs for therapy of bronchial asthma. [source] Increase in daytime symptoms is a sensitive and specific criterion for predicting corticosteroid-treated exacerbations in a clinical asthma trialCLINICAL & EXPERIMENTAL ALLERGY, Issue 3 2005S. M. Dennis Summary Background To determine which diary card variables are the most predictive for administration of additional courses of corticosteroids using the TRUST (The Regular Use of Salbutamol Trial) data set. Methods Logistic regression models were used to identify the extent to which a change in diary card variable affected the odds ratio (OR) for administering a course of oral or increased inhaled corticosteroids. The complete TRUST diary card data were used with over 200 000 days of diary card observations from 983 mild to moderate asthmatic subjects. Results An increase in daytime symptoms of 1,5 U over baseline was associated with an increase in the OR for starting all types of corticosteroids from two- to 60-fold. Conclusions These results indicate that an increase in daytime symptoms of two or more over baseline strongly predicts the administration of additional corticosteroids. The results have significant implications for both clinical practice and design of clinical trials in asthma. [source] Endogenous glucocorticoids and antigen-induced acute and late phase pulmonary responsesCLINICAL & EXPERIMENTAL ALLERGY, Issue 9 2000Stokes Peebles Background Several studies suggest that endogenous glucocorticoids can dampen the severity of experimental allergic reactions in animals. Objective To investigate the influence that endogenous glucocorticoids have on the course of IgE-mediated pulmonary early and late phase reactions. Methods Twenty-one allergic asthmatic and six healthy control subjects underwent inhaled antigen challenge with measurements of plasma cortisol and cortisone by gas chromatography-mass spectrometry. Results There were no differences between the asthmatic and control groups in the baseline levels of cortisol or cortisone. However, the asthmatic subjects had significantly higher cortisol levels (67.2 ± 8.6 vs 35.1 ± 4.5 ng/mL; P = 0.04) and had higher cortisol/cortisone ratios (4.8 ± 0.6 vs 3.0 ± 0.2; P = 0.01) 8 h after challenge compared to the control subjects. Among the asthmatic subjects, those whose FEV1 recovered rapidly had higher baseline levels of cortisol and those who displayed a late phase reaction had lower levels of cortisol during the late phase period. Conclusion The results suggest that endogenous glucocorticoids may play a significant role in the modulation of airway responses to antigen challenge, and that antigen challenge may induce cortisol production in allergic subjects. [source] | ||||||||||