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Lung deposition and distribution of flunisolide-HFA, assessed by Gamma Scintigraphy and Single Photon Emission Computed Tomography (SPECT)
$216
89
Abstracts
Role of Allergy and Inflammation in Nasal Polyps and Sinusitis
J. Hao% Y. Pang 2, D. Wang2; IOtolaryngology, National University of Singapore, Singapore, SINGAPORE, 2Department of Otolaryngology, National University of Singapore, Singapore, SINGAPORE. RATIONALE: The aim of this study was to determine the role of allergy and inflammation in nasal polyp and chronic sinusitis in Singapore patients. METHOD: The study included three groups: (1) pairs of nasal polyp and middle turbinate at the same side from 38 patients; (2) pairs of sinus mucosa and middle turbinate at the same side from 16 patients; (3) middle turbinates from 19 patients with septal deviation and without nasal allergy and infection, lmmunohistochemical staining with anti-CD4, antiCD8, anti-CDla, anti-CDl9, tryptase, major basic protein, neutrophil elastase were performed to determine the involvement of inflammatory cells. Total serum IgE and specific IgE to a common panel of allergen (Bermuda grass, Aspergillus famigatus, cockroach, D. pteronyssinus, D. farinea) were tested by RAST. RESULT: Cell patterns in nasal polyps/sinus mucosa and the turbinate from the same side were very similar with an infiltration of eosinophil, CD8+ cells, and mast cells in our patients. However, only eosinophil infiltration is significantly higher than the control group. There is no significant difference between the serum total IgE and specific IgE antibodies among the three groups. CONCLUSION: Our study demonstrates that nasal polyps and chronic sinusitis are inflammatory diseases, which are commonly associated with cytotoxic T-celts, eosinophils and mast cells. Eosinophil is the major infiltrated cell in these pathogenic conditions. A similar pattern of mucosal inflammation in middle turbinate and nasal polyps/sinusitis suggested a diffuse mucosa involvement. The role of IgE-mediated allergy does not appear to be a significant factor in sinusitis and polyp formation.
Funding: National Medical Research Council, Singapore
90 High Doses of the Novel Inhaled Steroid Cielesonide Have No Effect on HPA-axis Function in Patients with Moderate-toSevere Persistent Asthma
S. J. Szefler ], J. Herron 2, M. Lloyd 3, S. Rohatagi 3, J. E. Williams 3, S. Kundu 3, D. Banerji3; IPediatrics, National Jewish Medical & Research Center, Denver, CO, 2Arkansas Research Center, Little Rock, AR, 3Aventis.Pharmaceuticals, Bridgewater, NJ. RATIONALE: Potential systemic side effects associated with inhaled corticosteroids are a concern for asthmatic patients. The effects of inhaled ciclesonide (CIC) on cortisol suppression were evaluated by measuring 24-hour unstimulated serum cortisol. METHODS: Adult patients (N = 60, ->18 y) with moderate-to-severe persistent asthma were randomized to treatment for 4 weeks via metereddose inhaler (MDI), containing either chlorofluorocarbon (CFC) or hydrofluoroalkane (HFA) propellant, without spacer: ciclesonide 320 mg bid HFA-MDI (CTC320), ciclesonide 640 mg bid HFA-MDt (CIC640), ftuticasone propionate 440 mg bid CFC-MDI (FP440), fluticasone propionate 880 mg bid CFC-MDI (FP880), or placebo MD1. Baseline mean values for FEVI percent predicted ranged from 56.2-64.8 for all treatment groups. The primary endpoint, mean change from baseline in 24-hour serum cortisol area under the curve (AUC0-24h), was measured to evaluate hypothalamic-pituitary-adrenal-axis (HPA-axis) function. RESULTS: At week 4, mean serum cortisol AUC0-24h for the CIC640 group was not significantly different from placebo (P=0.7854), but decreased significantly from baseline for the FP880 group when compared with placebo (P<0.001) and CIC640 (P<0.01).
J ALLERGY CUN IMMUNOL FEBRUARY 2003
Serum cortisol AUC0.24h Placebo
CIC320
CIC640
FP440
FP880
Mean change -3.3 8.0 -8.9 10.0 -78. t (pg hr/dL) (-33.7, 27.2) (-20.5, 36.4)(-37.4. 19.5) (-18.9, 38.8)(-107.0, ~-9.1) (95% CI) % Change -1.3 4.2 4.5 4.8 -39.8 from baseline P value -0.597 0.785 0.541 0.001 (compared with placebo)
bid, Twice daily. CONCLUSIONS: High doses of ciclesonide, up to 1280 lag daily, are safe in the treatment of moderate-to-severe persistent asthma as demonstrated by lack of suppression of HPA-axis function.
Funding: Aventis
591 ,u. Deposition and Distribution of Flunisolide-HFA,Assessed by Gamma Scintigraphy and Single Photon Emission Computed Tomography (SPECT) S. P. Newman ], D. A. Clark ], C. S. Kalirai% G. R. Pitcairn 1, P. H. Hirst ], W. T. Abramowitz 2, R, Kapil 2, J. Rosenberg 2, K. Newman2; ]Pharmaceutical Profiles, Nottingham, UNITED KINGDOM, 2Forest Laboratories, New York, NY. RATIONALE: A new hydrofluoroalkane (HFA)- 134a formulation of flunisolide produces a particle size that is smaller ( 1.2 gin) than the chlorofluorocarbon (CFC) formulation of flunisolide (3.8 tam). This study was designed to assess whether the deposition of flunisolide-HFA (85 lag/puff) reaches the peripheral airways of the lungs, when delivered from a pressurized metered dose inhaler (pMDI) with built-in spacer. FlunisolideCFC (250 lag/puff) was used as a comparator. METHODS: In a 2-way crossover design, the deposition and distribution of fiunisolide from HFA and CFC pMDIs was compared in 12 asthmatics using a combination of two-dimensional gamma scintigraphic imaging and three-dimensional SPECT imaging. RESULTS: Mean (SD) whole lung deposition (by gamma scintigraphy) was significantly greater for flunisolide-HFA than for flunisolide-CFC (56.8 (6.1)% versus 15.3 (6.3)% of ex-device dose, respectively, P<0.01), and far less drug was deposited in the oral cavity. Preliminary analysis of the SPECT results revealed that the amount of drug deposited in the central airways was similar for both formulations. However, flunisolide-HFA provided greater peripheral lung zone deposition than flunisolide-CFC, with an increase in the peripheral/central lung zone deposition ratio of 46% (2.70 (0.97) versus 1.85 (0.63) respectively, P<0.01). CONCLUSIONS: Flunisolide-HFA provides superior lung deposition to flunisolide-CFC, distributes drug throughout the lungs, and effectively reaches small airways inflammation, which may provide additional clinical benefits.
Funding: Industry
92 Anti-inflammatory Effect of Teeastemizole on Nasal Epithelial Cell (NEC) Production of IL-8, IL-113,and Nitric Oxide (NO) M. F r i e d ], B. May2; ]Division of Allergy Immunology, Department of Medicine and Pediatrics, Nassau University Medical Center, East Meadow, NY, 2Microbiology, New York College of Osteopathic Medicine, New York Institute of Technology, Old Westbury, NY. RATIONALE: Antihistamines can have anti-inflammatory effects by inhibiting various cytokines or binding with epithelial cell derived mediators. We demonstrated that Astemizole decreased IL-let, IL-8 and NO in nasal
89
Abstracts
Role of Allergy and Inflammation in Nasal Polyps and Sinusitis
J. Hao% Y. Pang 2, D. Wang2; IOtolaryngology, National University of Singapore, Singapore, SINGAPORE, 2Department of Otolaryngology, National University of Singapore, Singapore, SINGAPORE. RATIONALE: The aim of this study was to determine the role of allergy and inflammation in nasal polyp and chronic sinusitis in Singapore patients. METHOD: The study included three groups: (1) pairs of nasal polyp and middle turbinate at the same side from 38 patients; (2) pairs of sinus mucosa and middle turbinate at the same side from 16 patients; (3) middle turbinates from 19 patients with septal deviation and without nasal allergy and infection, lmmunohistochemical staining with anti-CD4, antiCD8, anti-CDla, anti-CDl9, tryptase, major basic protein, neutrophil elastase were performed to determine the involvement of inflammatory cells. Total serum IgE and specific IgE to a common panel of allergen (Bermuda grass, Aspergillus famigatus, cockroach, D. pteronyssinus, D. farinea) were tested by RAST. RESULT: Cell patterns in nasal polyps/sinus mucosa and the turbinate from the same side were very similar with an infiltration of eosinophil, CD8+ cells, and mast cells in our patients. However, only eosinophil infiltration is significantly higher than the control group. There is no significant difference between the serum total IgE and specific IgE antibodies among the three groups. CONCLUSION: Our study demonstrates that nasal polyps and chronic sinusitis are inflammatory diseases, which are commonly associated with cytotoxic T-celts, eosinophils and mast cells. Eosinophil is the major infiltrated cell in these pathogenic conditions. A similar pattern of mucosal inflammation in middle turbinate and nasal polyps/sinusitis suggested a diffuse mucosa involvement. The role of IgE-mediated allergy does not appear to be a significant factor in sinusitis and polyp formation.
Funding: National Medical Research Council, Singapore
90 High Doses of the Novel Inhaled Steroid Cielesonide Have No Effect on HPA-axis Function in Patients with Moderate-toSevere Persistent Asthma
S. J. Szefler ], J. Herron 2, M. Lloyd 3, S. Rohatagi 3, J. E. Williams 3, S. Kundu 3, D. Banerji3; IPediatrics, National Jewish Medical & Research Center, Denver, CO, 2Arkansas Research Center, Little Rock, AR, 3Aventis.Pharmaceuticals, Bridgewater, NJ. RATIONALE: Potential systemic side effects associated with inhaled corticosteroids are a concern for asthmatic patients. The effects of inhaled ciclesonide (CIC) on cortisol suppression were evaluated by measuring 24-hour unstimulated serum cortisol. METHODS: Adult patients (N = 60, ->18 y) with moderate-to-severe persistent asthma were randomized to treatment for 4 weeks via metereddose inhaler (MDI), containing either chlorofluorocarbon (CFC) or hydrofluoroalkane (HFA) propellant, without spacer: ciclesonide 320 mg bid HFA-MDI (CTC320), ciclesonide 640 mg bid HFA-MDt (CIC640), ftuticasone propionate 440 mg bid CFC-MDI (FP440), fluticasone propionate 880 mg bid CFC-MDI (FP880), or placebo MD1. Baseline mean values for FEVI percent predicted ranged from 56.2-64.8 for all treatment groups. The primary endpoint, mean change from baseline in 24-hour serum cortisol area under the curve (AUC0-24h), was measured to evaluate hypothalamic-pituitary-adrenal-axis (HPA-axis) function. RESULTS: At week 4, mean serum cortisol AUC0-24h for the CIC640 group was not significantly different from placebo (P=0.7854), but decreased significantly from baseline for the FP880 group when compared with placebo (P<0.001) and CIC640 (P<0.01).
J ALLERGY CUN IMMUNOL FEBRUARY 2003
Serum cortisol AUC0.24h Placebo
CIC320
CIC640
FP440
FP880
Mean change -3.3 8.0 -8.9 10.0 -78. t (pg hr/dL) (-33.7, 27.2) (-20.5, 36.4)(-37.4. 19.5) (-18.9, 38.8)(-107.0, ~-9.1) (95% CI) % Change -1.3 4.2 4.5 4.8 -39.8 from baseline P value -0.597 0.785 0.541 0.001 (compared with placebo)
bid, Twice daily. CONCLUSIONS: High doses of ciclesonide, up to 1280 lag daily, are safe in the treatment of moderate-to-severe persistent asthma as demonstrated by lack of suppression of HPA-axis function.
Funding: Aventis
591 ,u. Deposition and Distribution of Flunisolide-HFA,Assessed by Gamma Scintigraphy and Single Photon Emission Computed Tomography (SPECT) S. P. Newman ], D. A. Clark ], C. S. Kalirai% G. R. Pitcairn 1, P. H. Hirst ], W. T. Abramowitz 2, R, Kapil 2, J. Rosenberg 2, K. Newman2; ]Pharmaceutical Profiles, Nottingham, UNITED KINGDOM, 2Forest Laboratories, New York, NY. RATIONALE: A new hydrofluoroalkane (HFA)- 134a formulation of flunisolide produces a particle size that is smaller ( 1.2 gin) than the chlorofluorocarbon (CFC) formulation of flunisolide (3.8 tam). This study was designed to assess whether the deposition of flunisolide-HFA (85 lag/puff) reaches the peripheral airways of the lungs, when delivered from a pressurized metered dose inhaler (pMDI) with built-in spacer. FlunisolideCFC (250 lag/puff) was used as a comparator. METHODS: In a 2-way crossover design, the deposition and distribution of fiunisolide from HFA and CFC pMDIs was compared in 12 asthmatics using a combination of two-dimensional gamma scintigraphic imaging and three-dimensional SPECT imaging. RESULTS: Mean (SD) whole lung deposition (by gamma scintigraphy) was significantly greater for flunisolide-HFA than for flunisolide-CFC (56.8 (6.1)% versus 15.3 (6.3)% of ex-device dose, respectively, P<0.01), and far less drug was deposited in the oral cavity. Preliminary analysis of the SPECT results revealed that the amount of drug deposited in the central airways was similar for both formulations. However, flunisolide-HFA provided greater peripheral lung zone deposition than flunisolide-CFC, with an increase in the peripheral/central lung zone deposition ratio of 46% (2.70 (0.97) versus 1.85 (0.63) respectively, P<0.01). CONCLUSIONS: Flunisolide-HFA provides superior lung deposition to flunisolide-CFC, distributes drug throughout the lungs, and effectively reaches small airways inflammation, which may provide additional clinical benefits.
Funding: Industry
92 Anti-inflammatory Effect of Teeastemizole on Nasal Epithelial Cell (NEC) Production of IL-8, IL-113,and Nitric Oxide (NO) M. F r i e d ], B. May2; ]Division of Allergy Immunology, Department of Medicine and Pediatrics, Nassau University Medical Center, East Meadow, NY, 2Microbiology, New York College of Osteopathic Medicine, New York Institute of Technology, Old Westbury, NY. RATIONALE: Antihistamines can have anti-inflammatory effects by inhibiting various cytokines or binding with epithelial cell derived mediators. We demonstrated that Astemizole decreased IL-let, IL-8 and NO in nasal