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Fenoterol in Children with Severe Asthma Exacerbation
AB94 Abstracts
296
Blockade of Costimulatory Signal Enhanced Glucocorticoid Suppression of T Cell-Induced Eosinophilia
SUNDAY
Akio Mori, MD, PhD1, Satoshi Kouyama1, Miyako Yamaguchi1, Akemi Ohtomo-Abe1, Yosuke Kamide1, Hiroaki Hayashi1, Kentaro Watai1, Chihiro Mitsui, MD1, Kiyoshi Sekiya, MD1, Takahiro Tsuburai, MD, PhD1, Masami Taniguchi, MD, PhD1, Takayuki Ohtomo, PhD2, and Osamu Kaminuma, PhD3; 1National Hospital Organization, Sagamihara National Hospital, Sagamihara, Japan, 2Tokyo University of Pharmacy and Life Science, Department of Pharmacotherapeutics, Tokyo, Japan, 3 The Center for Life Science Research, University of Yamanashi, Chuo, Japan. RATIONALE: To investigate the role of CD28 signal on the steroid responsiveness in asthma, effects of CTLA4-Ig and glucocorticoid on T cell activation and asthma model was analyzed. METHODS: Ovalbumin (OVA) specific murine helper T cell (Th) clones were derived from either the regional lymphnodes of Balb/c mice immunized with OVA/CFA or splenocytes of DO11.10 transgenic mice expressing T cell receptor specific for OVA/H-2d. To analyze steroid responsiveness in vitro, Th clones were cultured with antigen presenting cells and OVA in the presence of various concentration of dexamethasone (DEX). Proliferative responses of were measured by 3H-thymidine incorporation. For in vivo analysis, unprimed BALB/c mice were transferred with Th clones, challenged with OVA, and administered with DEX subcutaneously. Bronchoalveolar lavage fluid (BALF) was obtained 48 hour after challenge, and the number of infiltrating cells was differentially counted. CTLA4-Ig was administered intravenously. RESULTS: Steroid sensitive (SS) and steroid resistant (SR) clones were selected based on the effect of DEX on the proliferative responses of antigen-stimulated Th clones. Airway infiltration of eosinophils of mice transferred with SS clones were effectively inhibited by the administration of DEX. In contrast, those of mice transferred with SR clones were not significantly inhibited by DEX. Administration of CTLA4-Ig significantly suppressed the proliferation of DEX-treated SR clones in vitro, and the eosinophil infiltration of SR asthma model transferred with SR clones in vivo. In addition, CTLA4-Ig and DEX synergistically suppressed BALF eosinophilia of mice transferred with SS clones. CONCLUSIONS: Costimulatory signal mediated through CD28 is involved in the steroid responsiveness both in vitro and in vivo.
297
Comparison Efficacy of Randomized Nebulized Magnesium Sulfate and Ipratropium Bromide/ Fenoterol in Children with Severe Asthma Exacerbation
Siriporn Wongwaree, MD; Queen Sirikit National Institute of Child Health, bangkok, Thailand. RATIONALE: In Thailand, nebulized ipratropium bromide/fenoterol, is widely used in addition to salbutamol for severe asthma exacerbation. Recently, nebulized MgSO4 is indicated in GINA 2015 as additive treatment for severe cases. However, there is limited childhood data showed efficacy of both drugs. The purpose of this study were (1) compare efficacy of nebulized MgSO4 and ipratropiumbromide/fenoterol (2) study adverse effect of both drugs in moderate to severe cases. METHODS: A prospective, double-blind, randomized, controlled trial study was conducted in 31, 2-18 year old, children with moderate to severe asthma exacerbation. Each patient were randomized to receive either three doses of nebulized MgSO4 or three doses of nebulized ipratropium bromide/fenoterol every 30 minutes after conventional treatment with 3 doses of nebulized salbutamol. The Pediatric Respiratory Assessment Measure (PRAM) score was measured at 0, 30, 60, 90, 120 and 240 minutes after the treatment. The adverse event and admission days were also evaluated. RESULTS: Fifteen patients received nebulized MgSO4 and sixteen received nebulized ipratropium bromide/fenoterol. We found no statistically significant difference between both groups in PRAM score at 0, 30,
J ALLERGY CLIN IMMUNOL FEBRUARY 2017
60, 90, 120 and 240 minutes and hospitalization (p>0.05). There were two nasal sting sensation and one vomiting found in 3 patients receiving nebulized MgSO4. CONCLUSIONS: Our study demonstrated similar efficacy of nebulized MgSO4 and ipratropium bromide/fenoterol among Thai children with moderate to severe asthmatic attack.
298
Once-daily Tiotropium Respimat® Add-on Therapy Has a Safety Profile Comparable with Placebo in Children and Adolescents
Mark L. Vandewalker, MD, FAAAAI1, Eckard Hamelmann2, Michael Engel3, Georges El Azzi3, Petra Moroni-Zentgraf4, Anna Unseld5, Christian Vogelberg6, and Stanley J. Szefler, MD, FAAAAI7; 1Clinical Research of the Ozarks, Columbia, MO, 2Evangelisches Krankenhaus Bielefeld, and Allergy Center of the Ruhr University, Bochum, Germany, 3 Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim am Rhein, Germany, 4Boehringer Ingelheim Pty Ltd, Sydney, Australia, 5Global Biometrics and Data Sciences, Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach an der Riss, Germany, 6University Hospital Carl Gustav Carus, Technical University of Dresden, Dresden, Germany, 7Children’s Hospital Colorado, Aurora, CO. RATIONALE: Once-daily tiotropium Respimat® (tioR) as add-on to maintenance therapy is efficacious with a predictable safety profile in adults with symptomatic asthma. This pooled analysis from trials in adolescents (RubaTinA-asthma®: 12-17 years) and children (CanoTinAasthma®: 6-11 years) with moderate persistent asthma assessed the safety of tioR versus placebo Respimat®(pboR). METHODS: Two 48-week, Phase III, randomized, double-blind, placebo-controlled, parallel-group trials. Patients received once-daily tioR 5 mg, tioR 2.5 mg, or pboR, each delivered as two puffs, as add-on to ICS (200-800 mg [RubaTinA-asthma®] or 200-400 mg [CanoTinA-asthma®] budesonide/equivalent) 6 LTRA. Patients had symptomatic asthma despite stable maintenance therapy with ICS 6 additional controllers for _4 weeks before screening. LABAs were not permitted during either trial. > AEs (preferred term) were recorded throughout the trials. RESULTS: 801 patients were randomized, 798 treated. Baseline demographics and disease characteristics were similar across treatment groups; mean exposure to tioR was 330.6 days. AEs were reported by 61.7%, 63.5%, and 63.6% of patients in the tioR 5 mg, tioR 2.5 mg, and pboR groups, respectively. Proportion of patients with drug-related AEs was low (1.5%, 0.4%, and 1.1%, respectively). There were no AEs leading to discontinuation in the tioR groups (two in the pboR group). Serious AEs occurred in 1.5%, 1.9%, and 3.0%, respectively. No deaths occurred. The most commonly reported AEs were asthma (worsening), decreased PEF, and nasopharyngitis. CONCLUSIONS: The safety and tolerability of once-daily tiotropium Respimat® as add-on to maintenance therapy are similar to placebo in patients aged 6-17 years with moderate asthma, comparing well with findings in adults.
296
Blockade of Costimulatory Signal Enhanced Glucocorticoid Suppression of T Cell-Induced Eosinophilia
SUNDAY
Akio Mori, MD, PhD1, Satoshi Kouyama1, Miyako Yamaguchi1, Akemi Ohtomo-Abe1, Yosuke Kamide1, Hiroaki Hayashi1, Kentaro Watai1, Chihiro Mitsui, MD1, Kiyoshi Sekiya, MD1, Takahiro Tsuburai, MD, PhD1, Masami Taniguchi, MD, PhD1, Takayuki Ohtomo, PhD2, and Osamu Kaminuma, PhD3; 1National Hospital Organization, Sagamihara National Hospital, Sagamihara, Japan, 2Tokyo University of Pharmacy and Life Science, Department of Pharmacotherapeutics, Tokyo, Japan, 3 The Center for Life Science Research, University of Yamanashi, Chuo, Japan. RATIONALE: To investigate the role of CD28 signal on the steroid responsiveness in asthma, effects of CTLA4-Ig and glucocorticoid on T cell activation and asthma model was analyzed. METHODS: Ovalbumin (OVA) specific murine helper T cell (Th) clones were derived from either the regional lymphnodes of Balb/c mice immunized with OVA/CFA or splenocytes of DO11.10 transgenic mice expressing T cell receptor specific for OVA/H-2d. To analyze steroid responsiveness in vitro, Th clones were cultured with antigen presenting cells and OVA in the presence of various concentration of dexamethasone (DEX). Proliferative responses of were measured by 3H-thymidine incorporation. For in vivo analysis, unprimed BALB/c mice were transferred with Th clones, challenged with OVA, and administered with DEX subcutaneously. Bronchoalveolar lavage fluid (BALF) was obtained 48 hour after challenge, and the number of infiltrating cells was differentially counted. CTLA4-Ig was administered intravenously. RESULTS: Steroid sensitive (SS) and steroid resistant (SR) clones were selected based on the effect of DEX on the proliferative responses of antigen-stimulated Th clones. Airway infiltration of eosinophils of mice transferred with SS clones were effectively inhibited by the administration of DEX. In contrast, those of mice transferred with SR clones were not significantly inhibited by DEX. Administration of CTLA4-Ig significantly suppressed the proliferation of DEX-treated SR clones in vitro, and the eosinophil infiltration of SR asthma model transferred with SR clones in vivo. In addition, CTLA4-Ig and DEX synergistically suppressed BALF eosinophilia of mice transferred with SS clones. CONCLUSIONS: Costimulatory signal mediated through CD28 is involved in the steroid responsiveness both in vitro and in vivo.
297
Comparison Efficacy of Randomized Nebulized Magnesium Sulfate and Ipratropium Bromide/ Fenoterol in Children with Severe Asthma Exacerbation
Siriporn Wongwaree, MD; Queen Sirikit National Institute of Child Health, bangkok, Thailand. RATIONALE: In Thailand, nebulized ipratropium bromide/fenoterol, is widely used in addition to salbutamol for severe asthma exacerbation. Recently, nebulized MgSO4 is indicated in GINA 2015 as additive treatment for severe cases. However, there is limited childhood data showed efficacy of both drugs. The purpose of this study were (1) compare efficacy of nebulized MgSO4 and ipratropiumbromide/fenoterol (2) study adverse effect of both drugs in moderate to severe cases. METHODS: A prospective, double-blind, randomized, controlled trial study was conducted in 31, 2-18 year old, children with moderate to severe asthma exacerbation. Each patient were randomized to receive either three doses of nebulized MgSO4 or three doses of nebulized ipratropium bromide/fenoterol every 30 minutes after conventional treatment with 3 doses of nebulized salbutamol. The Pediatric Respiratory Assessment Measure (PRAM) score was measured at 0, 30, 60, 90, 120 and 240 minutes after the treatment. The adverse event and admission days were also evaluated. RESULTS: Fifteen patients received nebulized MgSO4 and sixteen received nebulized ipratropium bromide/fenoterol. We found no statistically significant difference between both groups in PRAM score at 0, 30,
J ALLERGY CLIN IMMUNOL FEBRUARY 2017
60, 90, 120 and 240 minutes and hospitalization (p>0.05). There were two nasal sting sensation and one vomiting found in 3 patients receiving nebulized MgSO4. CONCLUSIONS: Our study demonstrated similar efficacy of nebulized MgSO4 and ipratropium bromide/fenoterol among Thai children with moderate to severe asthmatic attack.
298
Once-daily Tiotropium Respimat® Add-on Therapy Has a Safety Profile Comparable with Placebo in Children and Adolescents
Mark L. Vandewalker, MD, FAAAAI1, Eckard Hamelmann2, Michael Engel3, Georges El Azzi3, Petra Moroni-Zentgraf4, Anna Unseld5, Christian Vogelberg6, and Stanley J. Szefler, MD, FAAAAI7; 1Clinical Research of the Ozarks, Columbia, MO, 2Evangelisches Krankenhaus Bielefeld, and Allergy Center of the Ruhr University, Bochum, Germany, 3 Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim am Rhein, Germany, 4Boehringer Ingelheim Pty Ltd, Sydney, Australia, 5Global Biometrics and Data Sciences, Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach an der Riss, Germany, 6University Hospital Carl Gustav Carus, Technical University of Dresden, Dresden, Germany, 7Children’s Hospital Colorado, Aurora, CO. RATIONALE: Once-daily tiotropium Respimat® (tioR) as add-on to maintenance therapy is efficacious with a predictable safety profile in adults with symptomatic asthma. This pooled analysis from trials in adolescents (RubaTinA-asthma®: 12-17 years) and children (CanoTinAasthma®: 6-11 years) with moderate persistent asthma assessed the safety of tioR versus placebo Respimat®(pboR). METHODS: Two 48-week, Phase III, randomized, double-blind, placebo-controlled, parallel-group trials. Patients received once-daily tioR 5 mg, tioR 2.5 mg, or pboR, each delivered as two puffs, as add-on to ICS (200-800 mg [RubaTinA-asthma®] or 200-400 mg [CanoTinA-asthma®] budesonide/equivalent) 6 LTRA. Patients had symptomatic asthma despite stable maintenance therapy with ICS 6 additional controllers for _4 weeks before screening. LABAs were not permitted during either trial. > AEs (preferred term) were recorded throughout the trials. RESULTS: 801 patients were randomized, 798 treated. Baseline demographics and disease characteristics were similar across treatment groups; mean exposure to tioR was 330.6 days. AEs were reported by 61.7%, 63.5%, and 63.6% of patients in the tioR 5 mg, tioR 2.5 mg, and pboR groups, respectively. Proportion of patients with drug-related AEs was low (1.5%, 0.4%, and 1.1%, respectively). There were no AEs leading to discontinuation in the tioR groups (two in the pboR group). Serious AEs occurred in 1.5%, 1.9%, and 3.0%, respectively. No deaths occurred. The most commonly reported AEs were asthma (worsening), decreased PEF, and nasopharyngitis. CONCLUSIONS: The safety and tolerability of once-daily tiotropium Respimat® as add-on to maintenance therapy are similar to placebo in patients aged 6-17 years with moderate asthma, comparing well with findings in adults.