365 . Asthma : basic science and clinical studies

printing supported by . Visit Chiesi at Stand D.30 TUESDAY, SEPTEMBER 27TH 2011 tion of corticosteroids and cold bronchial hyperresponsiveness (CBH) in patients with bronchial asthma (BA). Aim: To define the role of target-cells sensitivity to corticosteroids in cold bronchial hyperresponsiveness development in BA. Methods: 44 patients with BA were recruited. The mean level of asthma control was 16.8±0.1 points (Asthma Control Test). The absorption of cortisol by blood lymphocytes (ACL) in the standard test “in vitro” with hydrocortisone before 3-minute isocapnic cold air (-20°C) hyperventilation (ICAH) was studied. CBH was diagnosed by the drop of FEV1 after ICAH ( FEV1)≥10% from initial value. Results: All the patients were divided into two groups: the 1st (28 persons) was with constant values of hormone absorption by lymphocytes, the 2nd (16 persons) had lower values. ACL values were (0.701±0.054)×10-4 mkg/1000 cells and (0.527±0.038)×10-4 mkg/1000 cells, respectively (p<0.01). CBH was found out in 22 patients of the 1st group and in 6 patients of the 2nd one (χ2=7.42; p<0.01). In the 1st group there was the biggest part of patients (87%) with a high degree of CBH ( FEV1>18.5%) and a mean level of CBH ( FEV1 within the range of 14.2-18.4%). The 2nd group had only low values of CBH ( FEV1 within the range of 10.0-14.1%). The risk of high degree of CBH in patients of the 2nd group was three times higher than in the 1st group: chances ratio was 3.45; 95% confidence interval 1.50-7.64 (p=0.0005). Conclusion: CBH in BA patients is associated with the decrease of transmembrane penetration of glucocorticoids into target cells. P3265 LSC 2011 Abstract: Effect of inhaled apocynin on reactive oxygen species concentrations in exhaled breath condensate of asthmatics Joanna Stefanska, Agata Sarniak, Anna Wlodarczyk, Milena Sokolowska, Zbigniew Doniec, Dariusz Nowak, Rafal Pawliczak. Department of Immunopathology, Medical University of Lodz, Lodz, PL Department of Clinical Physiology, Medical University of Lodz, Lodz, PL Department of Pneumonology, National Institute for Tuberculosis and Lung Diseases, Rabka, PL Reactive oxygen species (ROS) have a strong impact on homeostasis and are thought to play an important role in inflammation in asthma. The sources of oxidative stress in patients with chronic inflammatory lung diseases derive mainly from increased amounts of ROS and reactive nitrogen species (NOS), generated by airway cells. Apocynin is and agent which blocks NADPH oxidase the enzyme, responsible for ROS production. The anti-inflammatory activity of apocynin has been demonstrated in a variety of cells and animal models of inflammation. Therefore, considering apocynin activities, we investigated the effect of nebulized apocynin in 14 nonsmoking asthmatics, in placebo-controlled, cross-over design study. Effects of apocynin have been checked 30, 60 and 120 minutes after nebulization by collecting exhaled breath condensate (EBC) samples. Additionally, we investigated safety parameters. Apocynin significantly decreased H2O2 concentration in EBC in comparison to placebo after 60 and 120 min. (0.29 μM vs. 0.44 μM, and 0.27 μM vs. 0.4 μM, respectively). Moreover, apocynin significantly reduced NO2 concentration 30 and 60 min after nebulization (2.75 μM vs. 4.65 μM, and 2.5 μM vs. 4.05 μM, respectively) in comparison to placebo. Finally, apocynin caused a significant decrease of NO3 concentration in EBC after 60 and 120 min after administration, comparing to placebo (5.34 μM vs. 8.2 μM (60 min), and 5.3 μM vs. 8 μM, (120 min) respectively). No influence of apocynin on safety parameters, and no adverse effects has been observed. These data suggest that using apocynin might be a promising solution to alleviate inflammatory process, and probably, symptoms of inflammatory diseases. P3266 Quantitative proteomics on bronchial biopsies from asthma and COPD: Effects of budesonide treatment Serena O’Neil1, Brigita Sitkauskiene2, Agne Babusyte2, Algirda Krisiukeniene2, Kristina Stravinskaite-Bieksiene2, Raimundas Sakalauskas2, Carina Sihlbom3, Linda Ekerljung1, Elisabet Carlsohn3, Bo Lundbäck1, Jan Lötvall1. 1Krefting Research Centre, Department of Internal Medicine, University of Gothenburg, Gothenburg, Sweden; 2Department of Pulmonology and Immunology, Lithuanian University of Health Sciences, Kaunas, Lithuania; 3Proteomics Core Facility, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden The global proteome of individual bronchial biopsy material from asthma and COPD patients has not been fully ascertained. The aim was to determine if mechanisms of disease and responses to treatment can be detected in biopsies from patients with asthma and COPD, using a quantitative proteomics technology. Endobronchial biopsies, pre and post treatment, were taken from patients with asthma (n=12) and COPD (n=11), as well as non-smoking (n=3) and smoking (n=2) healthy controls. Patients were randomised to double blind treatment with either placebo or budesonide (800 μg daily for 3 months). Quantitative proteomics technology was used to identify and quantify biopsy proteins. Pathways analysis was conducted to identify global proteome differences. A total of 1937 proteins were identified from all subjects. Proteome differences in asthma and COPD and changes in response to treatment could be observed. Analysis of the global proteome of COPD revealed that the top protein network contained the function of connective tissue disorder and that metabolic pathways were most relevant. In comparison, the top network in asthma contained dermatological functions, with the pathways being more actin-based. Changes in the proteome could also be observed in response to treatment. The increased relevance of cellular biological processes and decrease of oxidative stress can be seen for both asthma and COPD. Of particular interest, hepatic fibrosis was more associated with the COPD proteome and is altered with budesonide treatment. These results show that proteome differences can be detected using quantitative proteomics technology on clinically relevant biopsies from individual patients. P3267 The interplay of LXA4 and glucocorticoid receptor-based mechanisms in airway inflammation of childhood asthma Rosalia Gagliardo1, Stefania La Grutta3, Pascal Chanez2, Angelo Sala4, Liboria Siena1, Caterina Di Sano1, Loredana Riccobono1, Giovanni Viegi1, Mark Gjomarkaj1, Mirella Profita1. 1Institute of Biomedicine and Molecular Immunology, Italian National Research Council, Palermo, Italy; 2Département des Maladies Respiratoires, Université de la Méditerranée; INSERM-CNRS U600,UMR6212, Marseille, France; 3ARPA, Environmental Health Unit, Palermo, Italy; 4Department of Pharmacological Sciences, University of Milan,