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Bronchial Inflammation (bronchial + inflammation)
Selected AbstractsNoninvasive methods for assessment of airway inflammation in occupational settingsALLERGY, Issue 4 2010S. Quirce To cite this article: Quirce S, Lemière C, de Blay F, del Pozo V, Gerth Van Wijk R, Maestrelli P, Pauli G, Pignatti P, Raulf-Heimsoth M, Sastre J, Storaas T, Moscato G. Noninvasive methods for assessment of airway inflammation in occupational settings. Allergy 2010; 65: 445,458. Abstract The present document is a consensus statement reached by a panel of experts on noninvasive methods for assessment of airway inflammation in the investigation of occupational respiratory diseases, such as occupational rhinitis, occupational asthma, and nonasthmatic eosinophilic bronchitis. Both the upper and the lower airway inflammation have been reviewed and appraised reinforcing the concept of ,united airway disease' in the occupational settings. The most widely used noninvasive methods to assess bronchial inflammation are covered: induced sputum, fractional exhaled nitric oxide (FeNO) concentration, and exhaled breath condensate. Nasal inflammation may be assessed by noninvasive approaches such as nasal cytology and nasal lavage, which provide information on different aspects of inflammatory processes (cellular vs mediators). Key messages and suggestions on the use of noninvasive methods for assessment of airway inflammation in the investigation and diagnosis of occupational airway diseases are issued. [source] Masitinib, a c-kit/PDGF receptor tyrosine kinase inhibitor, improves disease control in severe corticosteroid-dependent asthmaticsALLERGY, Issue 8 2009M. Humbert Background:, Masitinib is a tyrosine kinase inhibitor targeting stem cell factor receptor (c-kit) and platelet-derived growth factor (PDGF) receptor, which are expressed on several cell types including mast cells and bronchial structural cells, respectively. We hypothesized that c-kit and PDGF receptor inhibition may decrease bronchial inflammation and interfere with airway remodeling, which are crucial features of severe asthma. Objectives:, The primary endpoint was the percent change from baseline in oral corticosteroids after 16 weeks of treatment. Change in asthma control (asthma control questionnaire), exacerbation rate, pulmonary function tests, rescue medication requirement and safety were secondary endpoints. Methods:, A 16-week randomized, dose-ranging (3, 4.5, and 6 mg/kg/day), placebo-controlled study was undertaken in 44 patients with severe corticosteroid-dependent asthma who remained poorly controlled despite optimal asthma management. Results:, At 16 weeks of treatment, a comparable reduction in oral corticosteroids was achieved with masitinib and placebo (median reduction of 78% and 57% in the masitinib and placebo arms, respectively). Despite this similar reduction, the Asthma Control Questionnaire score was significantly better in the masitinib arm as compared to placebo with a reduction by 0.99 unit at week 16 (P < 0.001) vs 0.43 unit in the placebo arm. Masitinib therapy was associated with more transient skin rash and edema. Conclusions:, Masitinib, a c-kit and PDGF-receptor tyrosine kinase inhibitor, may represent an innovative avenue of treatment in corticosteroid-dependent asthma. These preliminary results warrant further long-term clinical studies in severe asthma (ClinicalTrials.gov Identifier: NCT00842270). [source] Lipoxins in asthma: potential therapeutic mediators on bronchial inflammation?ALLERGY, Issue 10 2004C. Bonnans Arachidonic acid metabolism represents an important source of mediators with ambivalent actions. Among these, lipoxins (LXs) are the first agents identified and recognized as anti-inflammatory endogenous lipid mediators, which are involved in the resolution of inflammation and are present in the airways of asthmatic patients. Lipoxins result mainly from the interaction between 5 and 15-lipoxygenases (LO) and their levels are modulated by the degree of bronchial inflammation as well as by the long-term glucocorticoid treatments. In the airways, LX synthesis is higher in mild asthmatics than in severe asthmatics, whereas in vitro chemokine release inhibition by LXs is more effective in cells from severe asthmatics than from mild asthmatics. LipoxinA4 effects on interleukin (IL)-8 released by blood mononuclear cells and on calcium influx in epithelial cells are mediated by the specific receptor ALX. Lipoxin generation by lung epithelial cells depends mainly on 15-LO activity. Mild asthmatics present higher 15-LOb expression at the epithelium level than severe patients, whereas the LX deficit in severe asthma is associated with an up-regulation of the 15-LOa expressions. Therefore, bronchial epithelial cells become a target for therapeutic intervention and LXs represent a potential therapeutic solution for bronchial inflammation resolution in asthma. [source] Non-invasive markers of airway inflammation and remodeling in childhood asthmaPEDIATRIC ALLERGY AND IMMUNOLOGY, Issue 8 2009Rosalia Gagliardo To evaluate the relationship between pro-inflammatory and pro-remodeling mediators and severity and control of asthma in children, the levels of IL-8, MMP-9, TIMP-1 in induced sputum supernatants, the number of sputum eosinophils, as well as FeNO, were investigated in 35 asthmatic children, 12 with intermittent (IA) and 23 with moderate asthma (MA), and 9 controls (C). The patients with asthma were followed for 1 yr and sputum was obtained twice during the follow-up. Biomarker levels were correlated with the number of exacerbations. We found that IL-8, MMP-9, TIMP-1 and the numbers of eosinophils in induced sputum, as well as FeNO, were increased in children with IA and MA in comparison to C. The ongoing inflammation was confirmed by increased nuclear p65 NF-,B subunit localization in sputum cells. In MA, FeNO measurements, sputum eosinophils and IL-8 levels, positively correlated with the occurrence of disease exacerbations during a 1-yr follow-up. According to FeNO, sputum eosinophils and IL-8 sputum concentrations, and the number of exacerbations, two distinct phenotypes of MA were identified. This study shows that the presence of bronchial inflammation is detectable in the airways of some IA, as well as in the airways of MA, despite the regular ICS treatment. This study also proposes the need to perform large prospective studies to confirm the importance of measuring specific biomarkers in induced sputum, concomitantly to FeNO analyses, to assess sub-clinical airway inflammation and disease control in children with asthma. [source] Exhaled nitric oxide in asthmatic children and adolescents after nasal allergen challengePEDIATRIC ALLERGY AND IMMUNOLOGY, Issue 1 2005Christophe Pedroletti Epidemiological data suggest a comorbidity link between nasal and bronchial allergic disease. Exhaled nitric oxide (FENO) is a sensitive marker of bronchial inflammation and increases after bronchial allergen provocation. We studied FENO in 19 children and adolescents with allergic asthma and 10 controls before and 2, 6 and 24 h after a single nasal allergen challenge. The correlation between FENO and other markers of allergic inflammation, such as eosinophils in blood and eosinophil cationic protein (ECP) in serum and nasal lavage was also assessed. FENO remained unchanged 24 h post-challenge in both steroid and steroid-naïve patients. At 6 h post-challenge, FENO decreased in both asthmatics and controls. The asthmatic subjects showed a positive correlation between FENO and blood eosinophils before (r = 0.71, p = 0.001) and after the challenge, and between FENO and ECP in nasal lavage (r = 0.62, p = 0.02) 2 h after the challenge. Mean ECP in nasal lavage increased post-challenge but not significantly. We conclude that a single nasal allergen challenge does not augment bronchial inflammation although FENO, is related to blood eosinophil count and to the nasal inflammatory response. Our data do not support the theory of a direct transmission of the nasal inflammation to the lower airways. [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] Multiple tracheobronchial mucosal lesions in two cases of Churg,Strauss syndromeRESPIROLOGY, Issue 1 2006Hidekazu MATSUSHIMA Abstract: Churg,Strauss syndrome (CSS) is characterized by hypereosinophilia and a systemic necrotizing vasculitis seen almost exclusively in patients with asthma. The most common pathological findings in the chest in CSS are eosinophilic pneumonia, necrotizing vasculitis and granulomatous inflammation (extravascular granuloma). However, tracheobronchial mucosal lesions have rarely been reported in CSS. The authors report two patients with CSS who had multiple tracheobronchial mucosal lesions that were found by fibreoptic bronchoscopy. They were tiny nodular lesions and necrotizing bronchial inflammation with many eosinophils was observed upon pathological examination. The authors concluded that tracheobronchial mucosal lesions may be one of the manifestations of vasculitis seen in CSS. [source] Aggravation of bronchial eosinophilia in mice by nasal and bronchial exposure to Staphylococcus aureus enterotoxin BCLINICAL & EXPERIMENTAL ALLERGY, Issue 8 2006P. W. Hellings Summary Background The role of bacterial enterotoxins like Staphylococcus aureus enterotoxin B (SEB) in allergic asthma remains unknown. We used a mouse model of airway allergy to study the effects of nasal or bronchial contact with SEB on bronchial allergic inflammation. Methods The features of allergic asthma were induced in ovalbumin (OVA)-sensitized mice (days 1,13) by repeated exposures to nebulized OVA (days 33,37). Nasal or bronchial application of SEB was performed on three occasions (days 33,35,37), and the effects on bronchial inflammation, IgE titres and expression levels of mRNA for T helper type 2 cytokines and other inflammatory mediators were evaluated. Results Both nasal and bronchial SEB enhanced the allergen-induced bronchial inflammation, as reflected by more eosinophilic inflammation in the airway lumen and in bronchial tissue. Aggravation of experimental asthma correlated with higher expression of mRNA for IL-5, IL-4, IFN-,, IL-12 p40, eotaxin-1 and TGF-, in bronchi. In addition, nasal SEB elevated concentrations of IL-4, IL-5 and IFN-, in serum and bronchial SEB increased titres of OVA-specific and total IgE in serum. Conclusion Our data illustrate the potential of both nasal as well as bronchial SEB to aggravate several features of allergic asthma in a mouse model. [source] Measurement of nitric oxide and 8-isoprostane in exhaled breath of children with atopic eczemaCLINICAL & EXPERIMENTAL DERMATOLOGY, Issue 5 2009C. Zinelli Summary Background., Children with atopic eczema (AE) are at risk of developing asthma. Airway inflammation has been shown to be present before the onset of clinical asthma. Increased exhalation (forced expiration; FE) of nitric oxide (FENO) and 8-isoprostane seems to be a feature of bronchial inflammation in people with asthma. Aim., To determine whether the exhalation of these two molecules is increased in children with eczema, even in the absence of overt asthma. Methods., In total, 21 children with AE were recruited and compared with healthy controls. A questionnaire was completed to identify respiratory symptoms compatible with asthma. The severity of AE was graded clinically. Spirometry, FENO measurements and exhaled breath condensate collection for 8-isoprostane were performed. Results., The mean level of 8-isoprostane was similar for children with AE (2.33 ± 4.76 pg/mL) and controls (3.37 ± 3.43). FENO was increased in children with AE (mean 64.97 parts per billion) compared with the normal range, even in the absence of respiratory symptoms and in the presence of normal lung function. Conclusions., FENO but not 8-isoprostane levels in exhaled breath condensate are higher in children with AE without asthma. Our finding may indicate a predictive role for FENO for the development of asthma. [source] | ||||||||||