Thematic Poster Session Hall T UESDAY O CTOBER TH Asthma

Thematic Poster Session Hall 6.2-25 - 12:50-14:40 T UESDAY, O CTOBER 7 TH 2008 371. Asthma: mechanisms and treatment P3748 Aerobic exercise inhibit asthma features in mice Ronaldo Aparecido da Silva 1 , Rodolfo Paula Vieira 1 , Anna Cecilia Silva-Duarte 1 , Adenir Perini 2 , Fernanda Degobbi Tenorio Quirino dos Santos Lopes 2 , Milton Arruda Martins 2 , Celso Ricardo Fernandes de Carvalho 1 . 1 Physical Therapy, School of Medicine, University of Sao Paulo, Sao Paulo/Sao Paulo, Brazil; 2 Clinical Medicine, School of Medicine, University of Sao Paulo, Sao Paulo/Sao Paulo, Brazil Asthma induces bronchial inflammation, remodeling and increase airway resis- 658s Abstract printing supported by Nonin Medical, Inc. Visit Nonin Medical, Inc. at Hall 3.2 Stand 3.57 Thematic Poster Session Hall 6.2-25 - 12:50-14:40 T UESDAY, O CTOBER 7 TH 2008 Aim: to study blood content: some cytokines, metals, microelements in association with oxidation reduction status according to pathogenic form of bronchial asthma. Materials and methods: We examined bronchial asthma (n=38) and practically healthy subjects (n=20) in ages from 20 to 62 years. We marked the following BA pathogenic forms: atopic BA (ABA, n=20) and asthmatic triade (AT, n=18). Metal content (Cu, Zn, Ni, Fe) was determined by atom-absorption spectrophotometry; oxidation reduction status – by electronic spin resonance; cytokine concentration (IL-2, IL-4, IL-6, IFNγ) – by ELISA. Results: The IL-2 and IFNγ concentration was increased in both BA groups as compared to control. The IL-4 and IL-6 content was increased in ABA as compared to control. The results show two types of the immune response: with the predominance of Th2-dependent in ABA and Th1-dependent in AT. We found changes in the ratio Zn/Cu and Cu/Mn in both BA groups as compared to control. Higher level of methaemoglobin in BA reflects the intensification of lipoid peroxide oxidation, accompanied by lower activity of katalase and superoxide dysmutase (SOD) in erythrocytes, better expressed in AT. We marked correlation between Cu and ceruloplasmin content; Zn content and SOD level; Zn and free radicals content. Conclusion: The content of cytokines, metals, microelements in blood and reduction oxidation processes have their peculiarities depending from pathogenic form of bronchial asthma. tance. Aerobic exercise (AE) seems to have an important role in the treatment of asthmatic patients, however the mechanisms is unknown. This study evaluated, for the first time, the effect of AE after allergic airway inflammation already established. Balb/c mice were divided in 4 groups: Control, AE, Ovalbumin (OVA), and OVA+AE. Airway inflammation induced by (4 i.p. days 0, 14, 28, 42) followed by OVA aerosol (3×/w, 21-54th day). After that, exercise training started in a treadmill (5×/wk, 60 min, 4 weeks) in AE groups. OVA-sensitization was maintained until the 56th day when animals were euthanized. Lung mechanics, immunoglobulin levels and eosinophils counting were evaluated. Expression of CD3+ and CD4+ cells and Th1 (IL-2 and IFN-g) and Th2 (IL-4 and 5) cytokines and IL-10 was quantified after immunohistochemistry staining. OVA increased IgE and IgG1 levels, eosinophils counting and CD3+, CD4+, IL-4 and IL-5 expression (p<0.001; Figs. C-G, respectively). OVA also induced mucus production, increase in lung mechanic, collagen and elastin deposition and smooth muscle thickness (p<0.001; Figs. A, B, H-L, respectivey). AE decreased all parameters (p<0.01) and increased IL-10 expression (p<0.001). Our data strongly suggest that AE reduces Th2 response, IgE expression and airway remodeling and resistance even when airway inflammation is already established effects that might be mediated by IL-10. P3751 The influence of topical glucocorticoid on apoptosis of lymphocytes during allergic rhinitis Olga Ukhanova. Ministry of Health Care, Stavropol regional clinical Center, Stavropol, Russian Federation Objectives: Study of the topical glucocorticosteroid ability to modulate the lymphocytes apoptosis processes in nasal cavity mucosa and peripheral blood (PB) on the pattern of fluticasone propionate (FP). Methods: The AR patients were examined before and after FP therapy. The expression of Fas, Fas-L, Bcl-2 in rhinal secretion and PB was defined. All the data received were compared with the control group (CG). Results: During exacerbation the expression of CD95 and CD95L didn’t change in PB lymphocytes in comparison with the CG. Bcl-2 was 77,8±2,6% in the CG and increased up to 94±6,7% and 96±3,8% (p<0,001) according to the severity of illness. During the therapy of FP there was reliable reduction of Bcl-2 expression on the PB lymphocytes up to 87,61±0,28% and 87±1,03% (p<0,05) accordingly and that didn’t amount to the level of control value. The unilateral tendency to higher expression of CD95, CD95-L, Bcl-2 in comparison with the CG were observed in rhinal secretion lymphocytes. The effect of FP on the expression of CD95, CD95-L, Bcl-2 turned out to be opposite. One can observe the reduction of the expression of Bcl-2 under AR with mean degree 57.4±14.8% and grave condition from 90.1±4.3% to 15.9±5.1% and 14.1±4.5% (p<0.0001), that is considerably lower than the figures in CG. The same dynamics can be observed in the expression of CD95 and CD95-L. Conclusions: FP has no systemic effect that can be verified by the absence of reliable difference in CD95 and CD95-L synthesis of PB lymphocytes before and after therapy, and also by slight reduction of Bcl-2 expression on the PB lymphocytes during therapy in comparison with the expression on lymphocytes of target organ. P3749 Polymorphisms in CC16 and CCL26 genes and atopic bronchial asthma in Russian patients Elena Zaytseva 1 , Olga Voronko 1 , Elena Latysheva 2 , Nikolai Bodoev 1 , Gennady Storozhakov 2 , Alexander Archakov 1 . 1 Laboratory for Chemical Genomics, Research Institute of Biomedical Chemistry, Moscow, Russian Federation; 2 Dep.of Hospital Therapy II, Russian State Medical University, Moscow, Russian Federation Background: Asthma is a multifactorial disease with complex pathogenesis. Clara cell secretory protein (CC16) is produced by bronchiolar epithelial cells and acts as an immunosuppressive and antiinflammatory agent. Eotaxin-3 (CCL26) is a chemokine involved in eosinophilic inflammation in airways. The aim of the study was to investigate whether different genotypes of polymorphisms A38G in CC16 gene and 2497T/G in CCL26 gene contribute to atopic bronchial asthma in Russian patients. Methods: 283 patients with atopic bronchial asthma and 180 healthy individuals were examined. Asthma severity was estimated according to Global Initiative for Asthma (GINA) criteria.The genotyping was performed by MALDI-TOF mass spectrometry. Results: Allele A and genotype AA of polymorphic marker A38G (CC16) showed strong association with asthma development (OR = 1.52 and 2.39 respectively, p< 0.01) as well as with asthma severity (OR = 1.56 and 1.7 respectively). That risk factor was independent of gender, smoking status and age at the beginning of disease. No association was detected between polymorphism 2497T/G in CCL26 gene, asthma and asthma severity. Conclusion: Our findings suggest that polymorphism A38G in CC16 gene contribute to atopic bronchial asthma and asthma progression and may be helpful for differential approach to asthma therapy. Probably, polymorphism 2497T/G in CCL26 does not play a significant role in asthma development and its progession in Russian population. P3752 Haplotype analysis of interleukin 18 (IL-18) gene in Czech patients with allergic asthma Lydie Izakovicova Holla 1 , Marcel Schüller 2 , Dagmar Kindlova 3 , Vladimir Znojil 1 . 1 Department of Pathophysiology, Medical Faculty, Masaryk University, Brno, Czech Republic; 2 II. Children Clinic, Medical Faculty, Masaryk University and Faculty Hospital Brno, Brno, Czech Republic; 3 Clinic of Pulmonary Diseases and Tuberculosis, Faculty Hospital Brno, Brno, Czech Republic Background: Asthma is a chronic inflammatory disease of airways in which interleukin-18 (IL-18) plays an important role. Although IL-18 gene on chromosome 11q22 has been suggested a susceptibility gene for allergic diseases, there are controversial reports on IL-18 promoter variants as markers of asthma susceptibility. Aims: To test a possible role of IL-18 gene polymorphisms in a Czech population, case-control study including 284 patients with allergic asthma and 312 healthy control subjects was performed. Methods: An allele-specific polymerase chain reaction was used to analyze variants at positions -607 and -137 in the promoter 1 together with PCR-RFLP method for detection of polymorphism at position -133 in promoter 2 of the IL-18 gene. Results: There were no significant differences in the distribution of alleles or genotypes in any of three SNPs (−607C/A, −137G/C and −133C/G) in the IL-18 gene between controls and patients. Similarly, there was no relationship among the IL-18 genotypes and quantitative intermediate traits, such as total serum IgE levels. However, subsequent haplotype analysis revealed significant differences in haplotype frequencies between the patients with asthma and control subjects (p=0.035). Haplotype formed by – 607C, -137G and -133G alleles occurred significantly more frequently in asthmatics than in controls (0.068 vs. 0.035; p=0.01). P3750 The peculiarities of intercellular interactions and oxidation reduction status according to pathogenic form of bronchial asthma Svetlana Smirnova, Svetlana Kadricheva, Alla Kolpakova. Russian Academy of Medical Sciences, Siberian Division, State Medical Institute for Northern Problems, Krasnoyarsk, Russian Federation Inflammation in bronchial asthma (BA) is characterized by the cascade of processes with participation of wide variety of cells, factors and mediators. Their interactions form the typical pathology process. 659s Abstract printing supported by Nonin Medical, Inc. Visit Nonin Medical, Inc. at Hall 3.2 Stand 3.57 Thematic Poster Session Hall 6.2-25 - 12:50-14:40 T UESDAY, O CTOBER 7 TH 2008 Conclusions: Our results indicate that the three promoter polymorphisms in the IL-18 gene act in a cooperative fashion and suggest that IL-18 haplotypes could play a role in the pathogenesis of allergic asthma in a Czech population. This study was supported by the grant 310/06/0827 from the Grant Agency of the Czech Republic. 150 IU/mL (low) and 508 had IgE levels ≥ 150 (high).Mean ± SE predicted FEV1 was worse in patients with high IgE levels across all groups: 12- 17 years, 80.2±1.5% vs 86.5±2.5%; and 18 + years: 70.4±0.5% vs 76.3±0.5%. Mean ± SE post bronchodilation improvement in FEV1 was significantly better in the high IgE level group compared with the low IgE level group across all age groups: 12-17 years,12.5±0.9% vs 6.7±2.4% and 18 + years,10.9±0.7% vs 6.5±0.5%. Conclusions: Patients with IgE levels ≥150 IU/mL had lower lung function than those with IgE levels ≤ 150 IU/mL. Patients with IgE ≥ 150 IU/mL demonstrated greater responsiveness to bronchodilators, suggesting that allergic IgE driven mechanisms may enhance the reactivity of the airways. With the advent of omalizumab, it is important to rexamine the role of IgE testing in the diagnosis and management of extrinsic severe asthma. P3753 Thrombin stimulates the release of cytokines and histamine from basophils Aiko Yamaguchi 1 , Esteban Gabazza 2 , Atsushi Fujiwara 1 , Takehiro Takagi 1 , Hiroki Nakahara 1 , Hajime Fujimoto 1 , Hiroki Yasui 1 , Tetsu Kobayashi 1 , Hiroyasu Kobayashi 1 , Corina D’Alessandro-Gabazza 1 , Yoshiyuki Takei 3 , Osamu Taguchi 1 . 1 Pulmonary and Critical Care Medicine, Mie University Graduate School of Medicine, Tsu/Mie, Japan; 2 Immunology and Allergy Department, Mie University Graduate School of Medicine, Tsu/Mie, Japan; 3 Gastroenterology and Hepatology Department, Mie University Graduate School of Medicine, Tsu/Mie, Japan Background: Basophils plays a key role in allergic inflammation including bronchial asthma. Thrombin is a procoagulant factor that may also regulate the inflammatory response by stimulating the secretion of inflammatory mediators. The role of thrombin in allergic inflammation is unclear. Objective: This study evaluated the role of thrombin in the release of cytokines and histamine from basophils. To clarify whether thrombin action is mediated by protease-activated receptor (PAR)-1 in the release of these inflammatory mediators from KU-812 cells, the effect of PAR-1 agonist was also assessed. Methods: The human basophil cell line KU-812 was used in the assays. Cytokines and histamine were measured using immunoassays. Results: Thrombin significantly stimulated the secretion of interleukin (IL)-8, IL6, IL-13, and histamine from KU-812 cells. PAR-1 agonist stimulated the secretion of histamine in a dose-dependent manner. Conclusion: These results suggest that thrombin stimulates the secretion of IL-8, IL-6, IL-13, and histamine from basophils and that this action is mediated in part by its PAR-1 receptor. P3756 Cell biology of structural infringements of respiratory tract during allergic alteration Tatyana G. Barkhina, Valentina E. Golovanova, Mikhail Yu. Guschin. Cell Communication, Institute of Human Morphology, Moscow, Russian Federation; Cell Communication, Institute of Human Morphology, Moscow, Russian Federation; Cell Communication, Institute of Human Morphology, Moscow, Russian Federation Aim: To reveal the morphologic and biomolecular assessment of bronchial epithelium and alveolar parenchima at allergic rhinitis (AR), bronchial asthma (BA) and experimental allergic alteration. Material and methods: We investigated bronchobioptates (BB) from patients of different ages with AR and BA and experimental animal material of model allergic alteration. Light and electron microscopy and cytochemistry (ECC), immunohystochemistry (IHC) of markers of angiogenesis factor Willebrandt VIII and biomarker of actin smooth muscles. Reaction was regarded as positive in specific localization and species colouring for each antigen. The results of expression these markers were researched half-quantitatively in 3-marks scale. Results: By analysis semi-thin sections of bronchial epithelium, blood vessels and alveolar parenchima distinctive changes were demonstrated. Arteriolar wall was somewhere thickened because of endothelial hypertrophy and oedema, so that arteriolar lumen was decreased up to 40- 60%. Ultrastructural changes such as microclasmatosis and organelles destruction were found out in different cells of respiratory tract, endothelial cells and pericytes of blood capillaries. Signs of activity under influence allergic factor were revealed by the enzymes of cyclic nucleotides with help ECC. Biomarker of factor VIII was expressed in endotheliocytes of small vessels and capillars. Biomarker of SMA was expressed at the vessels of different calibers. Expression of these biomarkers was not the same during AR and BA. Conclusion: Our data prove that the complex methods give an opportunity to differentiate criterions of changes at allergic alteration of respiratory tract. P3754 Low energy laser irradiation in complex treatment of severe exacerbation of broncial asthma George Ivanov, Kvitoslava Mazhak, Iryna Platonova, Naiya Rudnycka. Department of Tuberculosis and Non-specific Lung Diseases, Lviv Scientific and Research Institute of Epidemiology and Hygiene, Lviv, Ukraine Goal: Discover the efficiency of intravenous laser irradiation of blood (ILIB) of different spectral modes with frequency modulations (FM) in basic bronchial asthma (BA) therapy. 81 patients with BA III in severe exacerbation phase after the course of intensive drug therapy went through ILIB of He-Cd laser (41 patients) and ILIB of He-Ne laser (40 patients). Procedures were held according to established methods. Efficiency was evaluated by studying the function of external respiration, clinical symptomatology dynamics, immunological and biochemical tests. During the control checkup after the end of the ILIB course there was almost no manifestation of BA, velocity parameters of respiration (Wilcox criteria) increased compared to course of intravenous introduction of corticosteroids (FEV1 increased by 47%, MIF50% by 80% and MIF75% by 100%). Rehabilitation of BA patients was full. Using lasers of different spectral modes facilitated decrease of cortisol level to normal, activated antioxidant potential of blood (in average SOD by 48%, ceruplasmin by 37%, catalase by 27%), increase of osmotic resistance of erythrocytes (Er) by 10-15%, decrease of Hb level, Er and leucocytes and context of CIC. During ILIB of He-Ne pool of T-helpers increased. ILIB of He-Cd facilitated increase of T-suppressers pool, absolute number of lymphocytes, quantity of E-POK rose with increased number of adsorbed erythrocytes, level of IgE decreased. Thus, use of ILIB with FM of He-Ne and He-Cd lasers is expedient in complex therapy of patients with BA, it has different impact, what enables us to differentiate the use of these methods, decrease drug therapy burden and speed up the achievement of stable remission process. P3757 Clinical implications of CCR5 expression and IL-2 secretion in bronchoalveolar lavage fluid in sarcoidosis J. Cemlyn-Jones 1 , S. Freitas 1 , T.M. Alfaro 1 , A. Henriques 2 , I. Silva 2 , A. Paiva 2 , L. Pais 2 , C. Robalo Codeiro 1 . 1 Centre of Pulmonology of Coimbra University Medical School, Coimbra University Medical School, Coimbra, Portugal; 2 Histocompatibility Centre of Coimbra, University Hospitals of Coimbra, Coimbra, Portugal Introduction: Pathogenesis of Sarcoidosis has been related to an increased production of Th1-like cytokines. However, this cytokine expression has not been systematically studied at a single-cell level. Aim: To evaluate the clinical use of immunophenotyping in bronchoalveolar lavage fluid (BALF) and peripheral blood (PB) through differential cell count, T-lymphocyte subsets and cytokine profile in Sarcoidosis. Methods: A prospective study was carried out over a fifteen month period in patients with suspected interstitial lung disease. Diagnosis of Sarcoidosis was established in 18 cases. Procedures performed were: macrophage/monocyte phenotypic characterization and quantification of CD13 and CD15 expression; percentage of naïve, effector and memory cells within CD4 and CD8 T-cell subsets; percentage of CD4 and CD8 T-cell subsets expressing CCR5; percentage of IL-2 producing T-cells. Clinical features, lung function and imaging were correlated with laboratory findings. Results: BALF cellular analysis showed a low macrophage/lymphocyte ratio. CD4/CD8 ratio was significantly high. The majority of CD4 T-cell subset showed a memory/effector phenotype. CCR5 was expressed in 69.5±25.3% and IL-2 was secreted in 28.3±15.2% of CD4 T-cells, whilst CD8 T-cells expressed CCR5 in 31.0±30.0% and secreted IL-2 in 23.2±13.8%. Conclusions: A low macrophage/lymphocyte ratio was found, with predominance of CD4+. Preliminary results suggest that there is an increase of CD4 and CD8 T-cells that express CCR5 and produce IL-2, possibly related to a Th1 pattern. In cases where CCR5 expression was more pronounced, patients also had more symptoms and lung function alterations. P3755 Use of IgE testing and lung function in diagnosing severe asthma Bashir Omarjee, Bernard Tanguy, Pascal Schlossmacher. Service de Maladies Respiratoires, Centre Hospitalier Régional F.Guyon, Saint Denis, Reunion Background: Immunoglobulin E (IgE) plays a key role in mediating the allergic response in asthma. The objective of this study was to evaluate the diagnostic value of serum IgE levels to the degree of severity of extrinsic asthma. Methods: Bronchodilation test was done in stable phase of illness (without respiratory symtoms), normal spirometry forced expiratory volume in 1s:FEV1 =80% of predicted values and total IgE was measured in 220 adolescents (mean age 15.25 years) and 330 adults patients (mean age 39.8 years), with extrinsic asthma (mild n=292,moderate n=206 and severe n=52). IgE data were analysed using a cut point of 150 IU/mL. Results: The value of total IgE in mild asthma was 220±229, in moderate 352±320 and in severe asthma was 845±622. A total of 142 patients had IgE levels < 660s Abstract printing supported by Nonin Medical, Inc. Visit Nonin Medical, Inc. at Hall 3.2 Stand 3.57 Thematic Poster Session Hall 6.2-25 - 12:50-14:40 T UESDAY, O CTOBER 7 TH 2008 P3758 A study of effects and mechanisms of LBP inhibitory peptide on the activation of macrophage induced by LPS Yunfeng Zhao 1 , Xueling Wu 2 . 1 Department of Pulmonary, Zhongda Hospital,Southeast University, Nanjing, Jiangsu Province, China; 2 Institute of Respiratory Disease, Xinqiao Hospital,Third Military University, Chongqing, China In our previous studies, we obtained phage clones with the sequence of WKXRKXFXKXXG (homologus with 91-102 aa of LBP) which could block the inflammatory activities of LBP, and synthesized peptide with the sequence of WKVRKSFFKLQG-NH2 (named as LBP inhibitory peptide, namely P12).We investigate whether P12 could reduce LPS induced inflammation in vivo. Methods: The affinity of P12 to LPS was determined by enzyme-linked immunosorbent assay (ELISA). Effect of P12 on the binding of FITC-LPS to U937 cells was determined by flow cytometric analysis (FACS). The expression of CD14 and TLR4 in U937 cells were detected by RT-PCR and Western blotting. NF-κB activation in U937 cells was evaluated with immuocytochemistry (ICC) and subunit P65 by Western blotting. The productions of TNF-α and nitric oxide (NO) were measured by ELISA and enzymatic assay with nitrate reductase. Results: The relative binding activity to LPS of P12 was higher than that of LBP in the same mass concentration. P12 markedly suppressed the binding of FITCLPS to U937 cells. P12 significantly reduced the expression of CD14 and TLR4 induced by LPS. NF-kappa B activation was inhibited in U937 cells challenged with low-dose LPS (100ng/ml) after P12 treatment. P12 treatment significantly reduced the production of TNF-α and NO in U937 cells induced by low-dose LPS. Conclusions: These studies suggest that LBP inhibitory peptide with the sequence of WKVRKSFFKLQG could inhibit the inflammatory function of LBP. These results indicate that LBP inhibitory peptide play a protective role in the activation of U937 cells induced by LPS through blocking the inflammatory site of LBP but not blocking the anti-inflammatory site. controlled asthma on the ending of 12 weeks of treatment and 36,7% of patients had characteristics of uncontrolled BA. The retrospective analysis of the clinical data and a complex of LCP parameters has shown, that at uncontrolled patients alongside with negative dynamics of clinical and functional features more essential disturbances of LCP parameters (lung capillary perfusion deficiency, less uniformly distributed lung perfusion with redistribution to the apical zones, low functional reserve opportunities of lung capillary circulation) are registered. It is shown, that the given parameters can be used as prognostic criteria, allowing allocate patients with uncontrolled BA. Conclusion: we suggest that lung microcirculation disturbance is one of the reasons of uncontrolled BA forming. P3759 Alveolar-capillary membrane dysfunction in heart failure: histopathological changes Felipe Muniz Zampieri 1 , Mauro Canzian 1 , Edwin Roger Parra 2 , Ronaldo Adib Kairalla 1 , Vera Luiza Capelozzi 2 . 1 Pathology, Instituto do Coração (InCor), São Paulo, Brazil; 2 Pahology, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil Background: In chronic heart failure (CHF) when the alveolar-capillary membrane is chronically challenged, remodeling of pathophysiologic and clinical parameters may take place. The resulting pulmonary histological changes in surgical lung biopsy specimens have been barely exploited. Method: Medical records of all patients with chronic heart failure and diffuse pulmonary infiltrates who underwent surgical lung biopsy from January 1982 to December 2005 were examined. Results: Twenty patients were men and 4 women, with a median age of 54 years (range 16 to 79 years). The main chronic heart faillure causes were myocardial ischemia, heart valve diseases, dilated cardiomiopathy, hypertensive cardiomiopathy, Chagas cardiomyopathy and constrictive pericarditis. Based on changes in alveolar-capillary barrier three main groups were created. Group I comprised acute pulmonary edema (APE), group II chronic capillary congestion (CCC) and group III diffuse alveolar damage (DAD). Acute cardiogenic pulmonary edema was associated to myocardial ischemia, chronic capillary congestion to heart valve disease and diffuse alveolar damage didn’t show any clinical picture predominance. Fifteen patients survived to be discharged and nine died in hospital. Conclusion: Alveolar-capillary injury in CHF is manifested through different patterns of histological changes which recognition can influence prognosis. Patients with CHF should be evaluated to establish treatment protocols for APE, CCC and DAD. Financial Support: FAPESP, CNPq, LIM05. P3760 Role of lung microcirculation disturbance in forming of uncontrolled bronchial asthma Julia O. Krylova. Laboratory of Prophylaxis of CRD, Far Eastern Scientific Center of Physiology and Pathology of Respiration, Blagoveschensk, Russian Federation Reasons of uncontrolled course of bronchial asthma (BA) are not completely known. Aim: to establish a possible role of lung capillary perfusion (LCP) reorganization in forming of uncontrolled course of bronchial asthma (BA). Methods: 30 patients with severe BA, received during three months standard basic therapy by the combined preparation (seretide, 100/1000 mkg/day) were under supervision. Inspection of patients was carried out before the beginning of treatment and through 12-week therapy and included: monitoring of clinical manifestatios, an estimation of lung function and the analysis of LCP changes by perfusion lung scintigraphy using macroaggregates of human serum albumin labeled with 99mTc. The activity distribution in the lung was evaluated at three different levels. Results: 63,3% of patients are corresponded to criteria of completely and partly 661s Abstract printing supported by Nonin Medical, Inc. Visit Nonin Medical, Inc. at Hall 3.2 Stand 3.57