Trials in asthma : asthma exacerbations and severe asthma P 1782 Use of steroid receptor related STIP 1 gene analysis as an asthma marker

printing supported by . Visit Chiesi at Stand B2.10 MONDAY, SEPTEMBER 3RD 2012 P1785 Association of glucocorticoid receptor gene polymorphisms of R23K and R477H and steroid-resistant asthma in Chinese Han population Feng Zhao, Haofeng Ouyang, Changgui Wu, Zhikui Li. Department of Respiratory, Xijing Hospital, Fourth Military Medical University, Xi’an, Shaanxi, China Some previous studies have shown that steroid resistance in asthma is associated with the mutation of glucocorticoid receptor (GR) gene. Other studies, however, have reached the opposite conclusion. The aim of this study was to detect the GR polymorphisms of R23K and R477H in steroid-resistant (SR) asthma patients and steroid-sensitive (SS) asthma patients in Chinese Han population, and to elucidate the association between GR polymorphisms and steroid resistance in asthma. Sixty-four SR patients and 68 SS patients were recruited for the detection of R23K and R477H variants, using polymerase chain reaction-sequence specific primers. Cortisol contents in serum were examined. The equilibrium dissociation constants (Kd) were calculated by dexamethasone radioligand-binding assay and Scatchard analysis to determine GR affinity to glucocorticoids. No statistically significant difference was found in the distribution of R23K polymorphism between SR patients and SS patients. In R477H, the wild genotype GG and AA frequencies were significantly lower in SR patients than in SS patients (P=0.043). The cortisol content in serum was found no significant difference between SR patients and SS patients, and among different genotypes. No significant differences in Kd were found between GG genotype and GA genotype of R23K variant, GG genotype and GA+GG genotype of R477H variant. In SR patients, the Kd values were significant higher than in SS patients (P<0.001). These findings suggest that GR polymorphisms of R23K and R477H exist in Chinese Han population. R477H variant is associated with steroid-resistant asthma in this population. P1786 The effect of single-nucleotide polymorphism in IL-13 on airway hyperresponsiveness in asthmatics Yu Utsumi, Takayuki Miyamoto, Kenshi Sekimura, Nobuhito Sasaki, Naomi Suzuki, Yutaka Nakamura, Hitoshi Kobayashi, Kohei Yamaucho. Internal Medicine, Iwate Medical University School of Medicine, Morioka, Iwate, Japan Background: Single-nucleotide polymorphism (SNP: rs20541) of IL-13 has been recognized as a risk factor of asthma. We recently demonstrated that FEV1 in asthmatics with the Q110 variant IL-13 declined faster (Allergol Int 2011). However, the effects of the variant IL-13 on airway hyperresponsiveness (AHR) have never been elucidated. Objectives: To evaluate the effects of SNP (rs20541) in IL-13 on AHR in asthmatics, we analyzed the relationship between SNP and AHR. Methods: We recruited 182 asthmatics to the current study who visited the asthma out-patient clinic in Iwate Medical University Hospital from 2006 to 2011. Subjects were genotyped using rs20541 by 7500 Fast Real-Time PCR System, (Applied Biosystems USA). Therapeutic steps (GINA 2011), eosinophil counts in peripheral blood and serum IgE concentration in those asthmatics were also studied. AHR to methacholine was measured by Astograph; Jupitor 21 (Chest, Japan). AHR was expressed as Dmin (U) (average ± SE). Statistical analysis was performed by one way ANOVA. This study was approved by the ethics committee of Iwate Medical University. Results: Genotyping of rs20541 showed that 26 A/A, 77 A/G and 79 G/G. D min (U) of the 3 genotypes was 1.17±0.300 in A/A, 1.99±0.35 in A/G and 2.85±0.39 in G/G. D min in the 3 genotypes was proved to be significantly different by Kruskal-Wallis One Way Analysis of Variance (p=0.007). There was no significant difference in therapeutic steps, eosinophil counts or serum IgE concentration among the 3 genotypes of asthmatics. Conclusion: SNP (rs20541) in IL-13 was associated with AHR, suggesting that IL-13 was involved in the progress of AHR through its biological activity on airway smooth muscles. P1787 Preventive effect of carbocysteine on exacerbation of asthma, GAIA randomised, placebo-controlled multi-centre study Hiroyuki Sano1, Yuji Tohda1, Mitsuru Adachi2, Takeshi Fukuda3, Ken Ohta4, Shunsuke Shoji5 , Terumasa Miyamoto6. 1Department of Respiratory Medicine and Allergology, Kinki University Faculty of Medicine, Osaka-Sayma, Japan; 2Division of Respiratory Medicine and Allergology, Department of Internal Medicine, Showa University School of Medicine, Tokyo, Japan; 3Department of Pulmonary Medicine and Clinical Immunology, Dokkyo Medical University, Mibu, Japan; 4Division of Respiratory Medicine & Allergology, Department of Medicine, Teikyo University School of Medicine, Tokyo, Japan; 5Clinical Department, National Hospital Organization Tokyo National Hospital, Kiyose, Japan; 6Internal Medicine and Allergology, Japan Clinical Allergy Research Institute, Tokyo, Japan Background: Management of exacerbation is clinically very important in asthma control. Carbocysteine, which improves airway mucus clearance and has antiinflammatory effects, including antioxidant effect, is expected to prevent asthma exacerbation in addition to COPD exacerbation. Objective: To evaluate the preventive effect of carbocysteine (C) on exacerbation in asthma patients using placebo (P) as a control. Methods: A total of 286 patients with mild to moderate asthma were randomly assigned to receive either C (1500mg/day) or P for 48 weeks. Patients were allowed to use long-term asthma control medications. The primary endpoint was annual frequency of exacerbations, and the secondary endpoints were pulmonary function and asthma control by ACQ. Results: At the time of enrollment, the disease type (atopic or non-atopic asthma) was significantly different (p = 0.02) between the two groups (C, n = 140; P, n = 140), but no statistically significant differences were observed in any other baseline characteristics of patients. The frequency of asthma exacerbations, the primary endpoint, was 5.40/year in the C group and 8.04/year in the P group, showing a significant decrease in the C group compared with the P group. The risk ratio of exacerbation was 0.658 (95% CI, 0.595-0.727; p < 0.001). No significant differences were observed in the pulmonary function or in the asthma control between the two groups. Conclusion: C significantly reduced the frequency of asthma exacerbations and thus provides a new therapeutic concept for long-term asthma management. P1788 Effect of fluticasone furoate (FF)/vilanterol (VI) once daily (OD) on risk of severe exacerbations in asthma Eric D. Bateman1, Paul M. O’Byrne2, William W. Busse3, Jan Lötvall4, Eugene R. Bleecker5, Leslie Andersen6, Brett Haumann7, Lucy Frith8, Jessica Lim8, Loretta Jacques7, Ashley Woodcock9. 1Department of Medicine, University of Cape Town, South Africa; 2Michael G DeGroote School of Medicine, McMaster University, Hamilton, Canada; 3Department of Medicine, University of Wisconsin, Madison, United States; 4Krefting Research Centre, University of Gothenburg, Sweden; 5Center for Genomics and Personalized Medicine, Wake Forest University Health Sciences, Winston-Salem, United States; 6Respiratory Medicines Development Center, GlaxoSmithKline, Research Triangle Park, United States; 7Respiratory Medicines Development Centre, GlaxoSmithKline, Uxbridge, United Kingdom; 8Quantitative Sciences Division, GlaxoSmithKline, Uxbridge, United Kingdom; 9School of Translational Medicine, University of Manchester, United Kingdom Introduction: FF is a novel inhaled corticosteroid in development for the treatment of asthma as a monotherapy and in combination with VI, a long-acting beta2 agonist. Objectives: To evaluate whether FF/VI significantly decreases the risk of severe asthma exacerbations vs FF. Methods: Patients (N=2019; ITT) received OD FF/VI 100/25mcg or FF 100mcg for ≥24 weeks (up to 76 weeks; study planned to finish after 330 events; event defined as a patient’s first on-treatment severe asthma exacerbation). Primary endpoint was time to first severe asthma exacerbation. Secondary endpoints: rate of severe asthma exacerbations per patient per year (PPPY) and change from baseline trough FEV1. Safety assessments included adverse events (AE), vital signs and number of hospitalisations due to a severe asthma exacerbation. Results: Compared with FF, FF/VI delayed the time to first severe exacerbation (hazard ratio 0.795 [95% CI: 0.642,0.985]; interim adj p=0.036). The adjusted probability of experiencing a severe exacerbation by 52 weeks was 12.8% for FF/VI and 15.9% for FF. PPPY rate was reduced (FF/VI 0.14 vs FF 0.19; p=0.014). There were greater improvements in trough FEV1 with FF/VI vs FF at Weeks 12, 36 and 52 (p<0.001). Incidence of treatment-related AEs: FF/VI 7%, FF 7% (on-treatment serious AEs: FF/VI 4%, FF 3%). Number of hospitalisations due to severe exacerbation was similar between treatments. There were no clinically relevant differences in vital sign assessments. Conclusions: FF/VI significantly reduced the risk of severe asthma exacerbations and improved lung function compared with FF alone. Safety and tolerability were similar between groups. Funded by GSK: HZA106837; NCT01086384. P1789 The value of magnesium sulfate nebulization in treatment of acute bronchial asthma during pregnancy Mohamed Badawy, Ibrahim Hasannen. Chest Department, South Valley University, Qena Faculty of Medicine, Luxor, Egypt Obestetric Department, Sohag University, Sohag, Egypt Little is known about the effect of inhaled Mg sulfate when added to B2 agonist in acute asthma with pregnancy. Objective: To evaluate the bronchodilator effect of nebulized magnesium sulfate with B2 agonist in the treatment of acute asthma during pregnancy, and its safety on pregnancy outcome. Material and methods: Patients were divided into two groups in a double blind randomization. Group A" received the routine treatment of acute asthma exacerbation plus nebulized salbut