- Email: [email protected]
−159 C to T polymorphism of CD14 is associated with non-atopic asthma and food allergy
J ALLERGY CLIN IMMUNOL VOLUME 111, NUMBER 2
29 Budesonide Symptom-Guided Adjustable Dosing Asthma Therapy with and Formoterol in a Single Inhaler--The ATAC0 Study R. BuhI l, E Kardos 2, A. Baare 3, K. Richter4, W. Meyer-Sabellek 3, B. Bruggenjurgen5, S. N. Willich 5, C. Vogelmeier6; JMedizinsche Klinik IlI, Mainz University Hospital, Mainz, GERMANY, 2Maingau Hospital, Frankfurt, GERMANY, 3AstraZeneca, Wedel, GERMANY, 4pulmonary Research Institute, Grol3hansdorf, GERMANY, 5Humboldt University, Berlin, GERMANY, 6Marburg University Hospital, Marburg, GERMANY. R A T I O N A L E : Budesonide and formoteroI in a single inhaler (Bud/Form) allows adjustment of doses of both corticosteroid and longacting beta2-agonist with the same inhaler to follow the variable course of the disease. This 16-week, randomized, parallel-group, open study compared the benefits of adjustable dosing with Bud/Form with fixed dosing on health-related quality of life (primary variable: standardized asthma quality of life questionnaire, AQLQ[S]), and symptom control (PEF, rescue medication, symptom severity, symptom-free days, nocturnal awakenings, severe exacerbations). METHODS: 3297 patients with mild-to-moderate persistent asthma were analyzed (56.4% female, mean age (• SEM) 37.4 _+ 10 years, PEF 355 1/min, APEF 22%). All patients received Bud/Form (160/4.5 gg) two inhalations bid for 4 weeks. Thereafter, patients receiving fixed dosing continued on Bud/Form two inhalations bid for 12 weeks. Patients receiving adjustable dosing stepped down to one inhalation bid. In the event of asthma worsening (predefined criteria), these patients doubled their dose to two or four inhalations bid for one week; the dose was reduced if the criteria for asthma worsening were not met at the end of the week. RESULTS: Despite a >30% lower mean dose (2.6 vs 3.8 inhalations per day, p<0.001 ), adjustable dosing was similarly effective as fixed dosing in improving AQLQ(S) score (+0.18 vs +0.2, respectively). Moreover, parameters of symptom control showed similar improvements in both groups (p=not significant for differences between groups). .CONCLUSIONS: Symptom-guided adjustable dosing with Bud/Form is feasible, and achieves similar improvements in quality of life and symptom control to fixed dosing at an overall lower dose.
Funding: AstraZeneca
230 olEfectASingle-Dose sthmaOf Inhaled Steroid on Nocturnal Worsening E. O. Vianna, G. Frezza, J. A. B. Martinez, J. Terra-Filho; Department of Medicine, University of S. Paulo Medical School at Ribeirfio Preto, Ribeirfio Preto, BRAZIL. RATIONALE: inhaled steroids are the most commonly used anti-inflammatory agents for asthma. They are increasingly recognized as having a more rapid onset of action than was thought. OBJECTIVE: To investigate the single-dose inhaled steroid effect on nocturnal worsening of asthma as a model for the detection of rapid effect of inhaled steroids. METHODS: Ten patients with steroid-naive moderate asthma and nocturnal asthma were recruited for this randomized, double-blind, placebocontrolled, crossover trial to test the effects of a single-dose (1000 mcg) of beclomethasone and fluticasone o n the nocturnal FEVI fall. The study consisted of three nights in our laboratory (one week apart). On each night, patients arrived to the hospital at 3:30 PM and underwent spirometry. At 4 PM. the subject received one of the three MDl-delivered treatments (placebo, beclomethasone 1000 mcg, or fluticasone 1000 mcg). Patients did not take any medication between 4:00 PM and 4:00 AM and spent the night in the hospital. Spirometry was then repeated at 4:00 AM. RESULTS: In the night following placebo administration, the overnight percentage fall (mean _+ SEM) in FEV1 was 24.2 +_ 7.7% in contrast to - l . 3 • 6.5% following fluticasone (p=0.008), and 5.8 -+ 6.3% following beclomethasone treatment (p=0.07 in comparison with placebo night). CONCLUSIONS: We found that a single-dose (within therapeutic range) of inhaled steroid reduced the FEVI fall seen in patients with nocturnal
Abstracts
$127
asthma when administered at 4 PM. Nocturnal worsening of asthma is a useful model for testing inhaled steroid activity in a single-night study.
Funding: FAPESP (S. Paulo State Government)
231 Asthmatics Treated with Preoperative Corticosteroids Have a Low Incidence of Perioperative Complications F. W. Su, D. Beckman, N. Masur, C. Kabalin, P. Yarnold, L. Grammer; Northwestern University, The Feinberg School of Medicine, Chicago, IL. RATIONALE: To establish the incidence of perioperative complications in asthmatic patients treated with preoperative corticosteroids and to compare these rates to the general surgical population at the same hospital. METHODS: Utilizing a retrospective cohort design, we studied 190 patients who underwent 249 procedures at our hospital between 1986 and 2002. Preoperative corticosteroids were administered in 240 of the procedures. The rate of asthma exacerbations, infections, wound infections, delayed wound healing, adrenocortical insufficiency, and mortality was assessed. RESULTS: Fourteen patients (5.6%) developed postoperative bronchospasm. Nine (3.6%) developed postoperative infections, 4 of which were wound infections (1.6%). There were no patients with adrenal insufficiency. One death occurred intraoperatively as a result of a neurosurgical complication. None of the complications could be predicted based on the attributes of our group. There was no statistical difference in the incidence of infections between our asthmatic population and the general surgical population in the same hospital. The incidence of wound infections was also not significant except in gynecologic procedures. CONCLUSIONS: Asthmatics who are treated with corticosteroids prior to undergoing surgery have a low incidence of complications.
Funding: Self-funded
232 -159 C to T Polymorphism of CD14 Is Associated with NonAtopic Asthma and Food Allergy J. G. Woo I, A. Assa'ad 2, A. Heizer 2, G. K. Khurana Hershey2; IDepartment of Environmental Health, Division of Epidemiology and Biostatistics, University of Cincinnati, Cincinnati, OH, 2Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH. RATIONALE: CD14, the receptor for lipopolysaccharide (LPS), plays an important role in innate immunity specific tbr LPS. We explored the relationship between a promoter polymorphism of CD 14 and atopic and non-atopic asthma and food allergy. METHODS: Patients with asthma and food allergy were recruited along with non-allergic, non-asthmatic control subjects. Atopic vs. non-atopic status was determined by skin test. The -159 C to T polymorphism was genotyped using PCR-based RFLP assay. RESULTS: The -159 T allele was more common among non-atopic asthma and food allergy patients than controls (X2=6.03, p=0.01 and X2=4.94, p=0.03, respectively). Food allergy patients had a 4-fold increased odds of having the T'l" genotype, vs. carriers of the C allele, compared with controls (Odds Ratio (OR)=3.9, 95% Confidence Interval (CI)=1.5-10.3), while non-atopic asthma patients had a 3-fold increased odds of TT (OR=3.1, 95% CI=1.1-9.1). Controlling for sex differences between groups, this relationship remained highly significant for food allergy (OR=3.7, 95% CI=1.4-10.1) and marginally significant for non-atopic asthma (OR=2.7, 95% CI=0.9-8.0). We performed a stratified analysis, limited to Caucasians, to reduce population stratification. The relationship with TT was stronger in Caucasian non-atopic asthma patients (OR=4.4, 95% CI= 1.3-14.8) and food allergy patients (OR=5.6, 95% Cl= 1.7-19.1), even adjusting for sex differences (OR=3.9, 95% C1=1.1-13.5 and OR=5.1, 95% CI=1.5-17.6, respectively). CONCLUSIONS: The TT genotype of the -159 C to T CDI4 potymorphism is associated with non-atopic asthma and food allergy, particularly in Caucasians. These findings suggest a novel relationship between innate immunity and allergy.
Funding: National Institutes of Health. NIAID:RO IAI46652-O IA I
29 Budesonide Symptom-Guided Adjustable Dosing Asthma Therapy with and Formoterol in a Single Inhaler--The ATAC0 Study R. BuhI l, E Kardos 2, A. Baare 3, K. Richter4, W. Meyer-Sabellek 3, B. Bruggenjurgen5, S. N. Willich 5, C. Vogelmeier6; JMedizinsche Klinik IlI, Mainz University Hospital, Mainz, GERMANY, 2Maingau Hospital, Frankfurt, GERMANY, 3AstraZeneca, Wedel, GERMANY, 4pulmonary Research Institute, Grol3hansdorf, GERMANY, 5Humboldt University, Berlin, GERMANY, 6Marburg University Hospital, Marburg, GERMANY. R A T I O N A L E : Budesonide and formoteroI in a single inhaler (Bud/Form) allows adjustment of doses of both corticosteroid and longacting beta2-agonist with the same inhaler to follow the variable course of the disease. This 16-week, randomized, parallel-group, open study compared the benefits of adjustable dosing with Bud/Form with fixed dosing on health-related quality of life (primary variable: standardized asthma quality of life questionnaire, AQLQ[S]), and symptom control (PEF, rescue medication, symptom severity, symptom-free days, nocturnal awakenings, severe exacerbations). METHODS: 3297 patients with mild-to-moderate persistent asthma were analyzed (56.4% female, mean age (• SEM) 37.4 _+ 10 years, PEF 355 1/min, APEF 22%). All patients received Bud/Form (160/4.5 gg) two inhalations bid for 4 weeks. Thereafter, patients receiving fixed dosing continued on Bud/Form two inhalations bid for 12 weeks. Patients receiving adjustable dosing stepped down to one inhalation bid. In the event of asthma worsening (predefined criteria), these patients doubled their dose to two or four inhalations bid for one week; the dose was reduced if the criteria for asthma worsening were not met at the end of the week. RESULTS: Despite a >30% lower mean dose (2.6 vs 3.8 inhalations per day, p<0.001 ), adjustable dosing was similarly effective as fixed dosing in improving AQLQ(S) score (+0.18 vs +0.2, respectively). Moreover, parameters of symptom control showed similar improvements in both groups (p=not significant for differences between groups). .CONCLUSIONS: Symptom-guided adjustable dosing with Bud/Form is feasible, and achieves similar improvements in quality of life and symptom control to fixed dosing at an overall lower dose.
Funding: AstraZeneca
230 olEfectASingle-Dose sthmaOf Inhaled Steroid on Nocturnal Worsening E. O. Vianna, G. Frezza, J. A. B. Martinez, J. Terra-Filho; Department of Medicine, University of S. Paulo Medical School at Ribeirfio Preto, Ribeirfio Preto, BRAZIL. RATIONALE: inhaled steroids are the most commonly used anti-inflammatory agents for asthma. They are increasingly recognized as having a more rapid onset of action than was thought. OBJECTIVE: To investigate the single-dose inhaled steroid effect on nocturnal worsening of asthma as a model for the detection of rapid effect of inhaled steroids. METHODS: Ten patients with steroid-naive moderate asthma and nocturnal asthma were recruited for this randomized, double-blind, placebocontrolled, crossover trial to test the effects of a single-dose (1000 mcg) of beclomethasone and fluticasone o n the nocturnal FEVI fall. The study consisted of three nights in our laboratory (one week apart). On each night, patients arrived to the hospital at 3:30 PM and underwent spirometry. At 4 PM. the subject received one of the three MDl-delivered treatments (placebo, beclomethasone 1000 mcg, or fluticasone 1000 mcg). Patients did not take any medication between 4:00 PM and 4:00 AM and spent the night in the hospital. Spirometry was then repeated at 4:00 AM. RESULTS: In the night following placebo administration, the overnight percentage fall (mean _+ SEM) in FEV1 was 24.2 +_ 7.7% in contrast to - l . 3 • 6.5% following fluticasone (p=0.008), and 5.8 -+ 6.3% following beclomethasone treatment (p=0.07 in comparison with placebo night). CONCLUSIONS: We found that a single-dose (within therapeutic range) of inhaled steroid reduced the FEVI fall seen in patients with nocturnal
Abstracts
$127
asthma when administered at 4 PM. Nocturnal worsening of asthma is a useful model for testing inhaled steroid activity in a single-night study.
Funding: FAPESP (S. Paulo State Government)
231 Asthmatics Treated with Preoperative Corticosteroids Have a Low Incidence of Perioperative Complications F. W. Su, D. Beckman, N. Masur, C. Kabalin, P. Yarnold, L. Grammer; Northwestern University, The Feinberg School of Medicine, Chicago, IL. RATIONALE: To establish the incidence of perioperative complications in asthmatic patients treated with preoperative corticosteroids and to compare these rates to the general surgical population at the same hospital. METHODS: Utilizing a retrospective cohort design, we studied 190 patients who underwent 249 procedures at our hospital between 1986 and 2002. Preoperative corticosteroids were administered in 240 of the procedures. The rate of asthma exacerbations, infections, wound infections, delayed wound healing, adrenocortical insufficiency, and mortality was assessed. RESULTS: Fourteen patients (5.6%) developed postoperative bronchospasm. Nine (3.6%) developed postoperative infections, 4 of which were wound infections (1.6%). There were no patients with adrenal insufficiency. One death occurred intraoperatively as a result of a neurosurgical complication. None of the complications could be predicted based on the attributes of our group. There was no statistical difference in the incidence of infections between our asthmatic population and the general surgical population in the same hospital. The incidence of wound infections was also not significant except in gynecologic procedures. CONCLUSIONS: Asthmatics who are treated with corticosteroids prior to undergoing surgery have a low incidence of complications.
Funding: Self-funded
232 -159 C to T Polymorphism of CD14 Is Associated with NonAtopic Asthma and Food Allergy J. G. Woo I, A. Assa'ad 2, A. Heizer 2, G. K. Khurana Hershey2; IDepartment of Environmental Health, Division of Epidemiology and Biostatistics, University of Cincinnati, Cincinnati, OH, 2Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH. RATIONALE: CD14, the receptor for lipopolysaccharide (LPS), plays an important role in innate immunity specific tbr LPS. We explored the relationship between a promoter polymorphism of CD 14 and atopic and non-atopic asthma and food allergy. METHODS: Patients with asthma and food allergy were recruited along with non-allergic, non-asthmatic control subjects. Atopic vs. non-atopic status was determined by skin test. The -159 C to T polymorphism was genotyped using PCR-based RFLP assay. RESULTS: The -159 T allele was more common among non-atopic asthma and food allergy patients than controls (X2=6.03, p=0.01 and X2=4.94, p=0.03, respectively). Food allergy patients had a 4-fold increased odds of having the T'l" genotype, vs. carriers of the C allele, compared with controls (Odds Ratio (OR)=3.9, 95% Confidence Interval (CI)=1.5-10.3), while non-atopic asthma patients had a 3-fold increased odds of TT (OR=3.1, 95% CI=1.1-9.1). Controlling for sex differences between groups, this relationship remained highly significant for food allergy (OR=3.7, 95% CI=1.4-10.1) and marginally significant for non-atopic asthma (OR=2.7, 95% CI=0.9-8.0). We performed a stratified analysis, limited to Caucasians, to reduce population stratification. The relationship with TT was stronger in Caucasian non-atopic asthma patients (OR=4.4, 95% CI= 1.3-14.8) and food allergy patients (OR=5.6, 95% Cl= 1.7-19.1), even adjusting for sex differences (OR=3.9, 95% C1=1.1-13.5 and OR=5.1, 95% CI=1.5-17.6, respectively). CONCLUSIONS: The TT genotype of the -159 C to T CDI4 potymorphism is associated with non-atopic asthma and food allergy, particularly in Caucasians. These findings suggest a novel relationship between innate immunity and allergy.
Funding: National Institutes of Health. NIAID:RO IAI46652-O IA I