- Email: [email protected]
Measured Onset of Bronchodilation With Budesonide and Formoterol Administered via One Pressurized Metered-dose Inhaler (pMDI) in Patients With Asthma Previously Receiving Inhaled Corticosteroids
Abstracts S249
J ALLERGY CLIN IMMUNOL VOLUME 119, NUMBER 1
974
Measured Onset of Bronchodilation With Budesonide and Formoterol Administered via One Pressurized Metered-dose Inhaler (pMDI) in Patients With Asthma Previously Receiving Inhaled Corticosteroids H. B. Kaiser1, C. J. Miller2, L. O’Dowd2; 1Clinical Research Institute, Minneapolis, MN, 2AstraZeneca, Wilmington, DE. RATIONALE: To evaluate measured onset of bronchodilation with budesonide/formoterol in a pMDI in patients with asthma previously receiving inhaled corticosteroids. METHODS: Two 12-week, randomized, double-blind, placebo-controlled, multicenter studies were conducted. Study I (SD-039-0717): after a 2-week run-in (2 inhalations bid budesonide pMDI 80 mg), patients with moderate-to-severe asthma received 2 inhalations bid budesonide/formoterol pMDI 160/4.5 mg (n5124), budesonide pMDI 160 mg 1 formoterol dry powder inhaler (DPI) 4.5 mg (n5115), budesonide pMDI 160 mg (n5109), formoterol DPI 4.5 mg (n5123), or placebo (n5125). Study II (SD-039-0716): after a 2-week run-in (current asthma therapy discontinued), patients with mild-to-moderate asthma received 2 inhalations bid budesonide/formoterol pMDI 80/4.5 mg (n5123), budesonide pMDI 80 mg (n5121), formoterol DPI 4.5 mg (n5114), or placebo (n5122). The time to achieve 15% FEV1 improvement after study medication was assessed. RESULTS: After the first dose of treatment (day of randomization [DOR]), the time to 15% FEV1 improvement was significantly (P<.001, Wilcoxon test) earlier with budesonide/formoterol pMDI versus budesonide pMDI and placebo and with formoterol DPI versus placebo in both studies. The percentages of patients achieving 15% FEV1 improvement within 15 minutes postdose on DOR were as follows: budesonide/formoterol pMDI (56.5% [I], 48.8% [II]); budesonide pMDI (5.5% [I], 5.8% [II]); formoterol DPI (56.9% [I], 57.0% [II]); budesonide pMDI 1 formoterol DPI (52.2% [I]); and placebo (5.6% [I], 8.2% [II]). CONCLUSIONS: Budesonide/formoterol pMDI demonstrated a rapid bronchodilatory response (within 15 minutes postdose), which is faster than budesonide pMDI or placebo and similar to formoterol DPI and budesonide pMDI 1 formoterol DPI. Funding: AstraZeneca
975
Effect of a Novel Medical Food (NMF) on Biomarkers of Inflammation and Airway Hyperresponsiveness in Children with Mild Persistent Asthma R. Covar1, B. Macomber1, L. Stewart1, M. Gleason1, K. Engelhardt1, J. Murphy1, A. Liu1, S. Wood2, S. DeMichele2, E. Gelfand1, S. Szefler1; 1 National Jewish Med Res Ctr, Denver, CO, 2Ross Products, Abbott Laboratories, Columbus, OH. RATIONALE: Diets enriched with eicosapentaenoic acid (EPA), gammalinolenic acid (GLA), and elevated antioxidants as a NMF can reduce pulmonary and systemic inflammation and improve clinical outcomes in critically ill patients. This observation prompted an efficacy and safety study of NMF in childhood asthma, another chronic inflammatory disease.
METHODS: 43 children from 6 to 14 years (mean 10.6) of age with mild persistent asthma not on controller therapy were randomized to receive either 8oz/day of NMF (n523) or an isocaloric, isonitrogenous control formula (n520) for 12 weeks with visits at 2, 4, 8, and 12 weeks to assess clinical, pulmonary function and biomarker measures. Values presented are means(6SEM) at final visit as percent change from baseline. P values are from the interaction term of a mixed linear model over serial observations. RESULTS: Daily consumption of NMF for 3 months as compared with control formula showed the following percent changes from baseline: exhaled nitric oxide [(1.0(11) vs. 64.9(26), p<0.04], % sputum eosinophils [-57.5(32) vs. 1204.5(137)], log PC20 [487.8(355) vs. 41.2(193)], and FEV1(L) [5.6(2.5) vs. 2.2(3.0)] with no differences in asthma-free days. After 2 to 4 weeks, peripheral blood mononuclear cell phospholipid fatty acid profiles showed significant (P<0.01) increases in the levels of EPA and docosahexaenoic acid and decrease in arachidonic acid in the NMF group as compared to control group. CONCLUSIONS: In children with mild asthma, NMF showed improvement in several objective biomarkers of inflammation and pulmonary function along with an immune cell fatty acid composition that reflects an antiinflammatory profile. Funding: Ross Products, Abbott Laboratories
976
The Significance of the Initiating Time of Inhaled Corticosteroid in Asthma Treatment J. Jung1, J. Kim2, J. Lee3; 1Dong-A University Hospital, Busan, REPUBLIC OF KOREA, 2Ulsan University Hospital, Ulsan, REPUBLIC OF KOREA, 3Masan Samsung Hospital, Masan, REPUBLIC OF KOREA. RATIONALE: Recurrent airway inflammation in asthma develops airway remodeling that makes irreversible imparement of lung function and decreases the response to the inhaled corticosteroids. In some reports, airway remodeling develops in the early period of asthma. We evaluated the effects of initiating time of inhaled corticosteroid in asthma treatment. METHODS: Fifty-five bronchial asthma patients who used inhaled corticosteroid(Seretide diskus 100 mg/Symbicort turbuhaler 80 mg) from 2003 to 2005 in Dong-A University Medical Center. Nineteen were started treatment within 1 year after initiating the asthma symptoms (Group A) and thirty-six were started treatment after 1 year. (Group B). We evaluated serum total IgE, total eosinophil count, specifie IgE to the Dp/Df. And we also evaluated FEV1/FVC, PEFR(morning & evening), symptom score (morning & evening) before treatment, at 2 weeks, 4 weeks after treatment. RESULTS: PC20 was higher in Group A (6.7864.93 mg/mL) than Group B (5.5964.80) but there was no significance. The positive rate of the specific IgE to the Dp/Df were lower in Group A (Dp 63.16%, Df 52.63%) than Group B (Dp 75.00%, Df 77.78%) but there was no significance. FEV1/ FVC before treatment was significantly higher in Group A (0.9360.07) than Group B (0.9160.05) (p50.042) and FEV1/FVC in 2 weeks after treatment was significantly higher in Group A (0.9560.03) than Group B (0.9260.06) (p50.037). There was significant difference in night symptom score in 4 weeks after treatment between Group A (0.266.45) and Group B (0.6160.64). CONCLUSIONS: Starting inhaled corticosteroid within 1 year after onset of asthma symptoms has good results in the improvement of lung function and symptom scores.
TUESDAY
RESULTS: The mean change in heart rate (-3.9-1.7 beats/minute), and respiratory rate (0.6-1.0 breaths/minute) was not significant for the three treatment groups. There was no statistical difference in mean QT (1.27.2 msec) and corrected QT (QTc range -0.58-4.3 msec; individual not >440msec) between Ventolin 90 mcg vs. placebo [p50.156 (QT); p50.285(QTc)] and Ventolin 180 mcg vs. placebo [p50.723 (QT); p50.420 (QTc)]. The change in PR interval (0.020-2.870msec) and QRS duration (-0.3-1.3) were not significant; PR interval: Ventolin 90 mcg vs. placebo; p50.826 and Ventolin 180 mcg vs. placebo; p50.876, and QRS duration: Ventolin 90 mcg vs placebo; p50.386 and Ventolin 180 mcg vs. placebo; p50.675. CONCLUSIONS: Ventolin 90mcg or 180mcg administered TID showed no significant changes in QT, QTc or PR interval, QRS duration and heart rate in this population. Funding: GlaxoSmithKline
J ALLERGY CLIN IMMUNOL VOLUME 119, NUMBER 1
974
Measured Onset of Bronchodilation With Budesonide and Formoterol Administered via One Pressurized Metered-dose Inhaler (pMDI) in Patients With Asthma Previously Receiving Inhaled Corticosteroids H. B. Kaiser1, C. J. Miller2, L. O’Dowd2; 1Clinical Research Institute, Minneapolis, MN, 2AstraZeneca, Wilmington, DE. RATIONALE: To evaluate measured onset of bronchodilation with budesonide/formoterol in a pMDI in patients with asthma previously receiving inhaled corticosteroids. METHODS: Two 12-week, randomized, double-blind, placebo-controlled, multicenter studies were conducted. Study I (SD-039-0717): after a 2-week run-in (2 inhalations bid budesonide pMDI 80 mg), patients with moderate-to-severe asthma received 2 inhalations bid budesonide/formoterol pMDI 160/4.5 mg (n5124), budesonide pMDI 160 mg 1 formoterol dry powder inhaler (DPI) 4.5 mg (n5115), budesonide pMDI 160 mg (n5109), formoterol DPI 4.5 mg (n5123), or placebo (n5125). Study II (SD-039-0716): after a 2-week run-in (current asthma therapy discontinued), patients with mild-to-moderate asthma received 2 inhalations bid budesonide/formoterol pMDI 80/4.5 mg (n5123), budesonide pMDI 80 mg (n5121), formoterol DPI 4.5 mg (n5114), or placebo (n5122). The time to achieve 15% FEV1 improvement after study medication was assessed. RESULTS: After the first dose of treatment (day of randomization [DOR]), the time to 15% FEV1 improvement was significantly (P<.001, Wilcoxon test) earlier with budesonide/formoterol pMDI versus budesonide pMDI and placebo and with formoterol DPI versus placebo in both studies. The percentages of patients achieving 15% FEV1 improvement within 15 minutes postdose on DOR were as follows: budesonide/formoterol pMDI (56.5% [I], 48.8% [II]); budesonide pMDI (5.5% [I], 5.8% [II]); formoterol DPI (56.9% [I], 57.0% [II]); budesonide pMDI 1 formoterol DPI (52.2% [I]); and placebo (5.6% [I], 8.2% [II]). CONCLUSIONS: Budesonide/formoterol pMDI demonstrated a rapid bronchodilatory response (within 15 minutes postdose), which is faster than budesonide pMDI or placebo and similar to formoterol DPI and budesonide pMDI 1 formoterol DPI. Funding: AstraZeneca
975
Effect of a Novel Medical Food (NMF) on Biomarkers of Inflammation and Airway Hyperresponsiveness in Children with Mild Persistent Asthma R. Covar1, B. Macomber1, L. Stewart1, M. Gleason1, K. Engelhardt1, J. Murphy1, A. Liu1, S. Wood2, S. DeMichele2, E. Gelfand1, S. Szefler1; 1 National Jewish Med Res Ctr, Denver, CO, 2Ross Products, Abbott Laboratories, Columbus, OH. RATIONALE: Diets enriched with eicosapentaenoic acid (EPA), gammalinolenic acid (GLA), and elevated antioxidants as a NMF can reduce pulmonary and systemic inflammation and improve clinical outcomes in critically ill patients. This observation prompted an efficacy and safety study of NMF in childhood asthma, another chronic inflammatory disease.
METHODS: 43 children from 6 to 14 years (mean 10.6) of age with mild persistent asthma not on controller therapy were randomized to receive either 8oz/day of NMF (n523) or an isocaloric, isonitrogenous control formula (n520) for 12 weeks with visits at 2, 4, 8, and 12 weeks to assess clinical, pulmonary function and biomarker measures. Values presented are means(6SEM) at final visit as percent change from baseline. P values are from the interaction term of a mixed linear model over serial observations. RESULTS: Daily consumption of NMF for 3 months as compared with control formula showed the following percent changes from baseline: exhaled nitric oxide [(1.0(11) vs. 64.9(26), p<0.04], % sputum eosinophils [-57.5(32) vs. 1204.5(137)], log PC20 [487.8(355) vs. 41.2(193)], and FEV1(L) [5.6(2.5) vs. 2.2(3.0)] with no differences in asthma-free days. After 2 to 4 weeks, peripheral blood mononuclear cell phospholipid fatty acid profiles showed significant (P<0.01) increases in the levels of EPA and docosahexaenoic acid and decrease in arachidonic acid in the NMF group as compared to control group. CONCLUSIONS: In children with mild asthma, NMF showed improvement in several objective biomarkers of inflammation and pulmonary function along with an immune cell fatty acid composition that reflects an antiinflammatory profile. Funding: Ross Products, Abbott Laboratories
976
The Significance of the Initiating Time of Inhaled Corticosteroid in Asthma Treatment J. Jung1, J. Kim2, J. Lee3; 1Dong-A University Hospital, Busan, REPUBLIC OF KOREA, 2Ulsan University Hospital, Ulsan, REPUBLIC OF KOREA, 3Masan Samsung Hospital, Masan, REPUBLIC OF KOREA. RATIONALE: Recurrent airway inflammation in asthma develops airway remodeling that makes irreversible imparement of lung function and decreases the response to the inhaled corticosteroids. In some reports, airway remodeling develops in the early period of asthma. We evaluated the effects of initiating time of inhaled corticosteroid in asthma treatment. METHODS: Fifty-five bronchial asthma patients who used inhaled corticosteroid(Seretide diskus 100 mg/Symbicort turbuhaler 80 mg) from 2003 to 2005 in Dong-A University Medical Center. Nineteen were started treatment within 1 year after initiating the asthma symptoms (Group A) and thirty-six were started treatment after 1 year. (Group B). We evaluated serum total IgE, total eosinophil count, specifie IgE to the Dp/Df. And we also evaluated FEV1/FVC, PEFR(morning & evening), symptom score (morning & evening) before treatment, at 2 weeks, 4 weeks after treatment. RESULTS: PC20 was higher in Group A (6.7864.93 mg/mL) than Group B (5.5964.80) but there was no significance. The positive rate of the specific IgE to the Dp/Df were lower in Group A (Dp 63.16%, Df 52.63%) than Group B (Dp 75.00%, Df 77.78%) but there was no significance. FEV1/ FVC before treatment was significantly higher in Group A (0.9360.07) than Group B (0.9160.05) (p50.042) and FEV1/FVC in 2 weeks after treatment was significantly higher in Group A (0.9560.03) than Group B (0.9260.06) (p50.037). There was significant difference in night symptom score in 4 weeks after treatment between Group A (0.266.45) and Group B (0.6160.64). CONCLUSIONS: Starting inhaled corticosteroid within 1 year after onset of asthma symptoms has good results in the improvement of lung function and symptom scores.
TUESDAY
RESULTS: The mean change in heart rate (-3.9-1.7 beats/minute), and respiratory rate (0.6-1.0 breaths/minute) was not significant for the three treatment groups. There was no statistical difference in mean QT (1.27.2 msec) and corrected QT (QTc range -0.58-4.3 msec; individual not >440msec) between Ventolin 90 mcg vs. placebo [p50.156 (QT); p50.285(QTc)] and Ventolin 180 mcg vs. placebo [p50.723 (QT); p50.420 (QTc)]. The change in PR interval (0.020-2.870msec) and QRS duration (-0.3-1.3) were not significant; PR interval: Ventolin 90 mcg vs. placebo; p50.826 and Ventolin 180 mcg vs. placebo; p50.876, and QRS duration: Ventolin 90 mcg vs placebo; p50.386 and Ventolin 180 mcg vs. placebo; p50.675. CONCLUSIONS: Ventolin 90mcg or 180mcg administered TID showed no significant changes in QT, QTc or PR interval, QRS duration and heart rate in this population. Funding: GlaxoSmithKline