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Oral Corticosteroid Use Increases the Risk of Glucocorticoid-related Adverse Events in Asthmatics
AB74 Abstracts
278
SUNDAY
Oral Corticosteroid Use Increases the Risk of Glucocorticoidrelated Adverse Events in Asthmatics J. L. Zazzali1, M. Broder2, E. Chang2; 1Genentech, Inc., South San Francisco, CA, 2Partnership for Health Analytic Research, Beverly Hills, CA. RATIONALE: Oral corticosteroids (OCS) are a mainstay of asthma therapy for managing severe symptoms and exacerbations. Prolonged systemic exposure to glucocorticoids is known to be associated with increased risk of glucocorticoid-related adverse events (GAEs). Our objective was to determine the risk of GAEs associated with cumulative OCS exposure in asthmatics. METHODS: Retrospective cohort analysis of adult asthmatics using a HIPAA-compliant claims database. Patients were continuously enrolled during 2002-2003 and were followed until the end of enrollment or study end (2007) whichever was earlier (median5 1,461 days observation). Patients with potential GAEs in the first year were excluded. Cox regression models estimated adjusted hazard ratios of the risk of GAEs (osteoporosis, fracture and cataracts) for different OCS exposure levels, measured by cumulative prednisone-equivalent dose as recorded on pharmacy claims, while adjusting for age, gender, region, usual care physician specialty, and chronic conditions. RESULTS: We examined 37,891 asthmatics (mean age544.9 years, 65.7% female). For every 1,000 mg increase in prednisone-equivalent OCS exposure, the risk of a claim for osteoporosis was 3% higher (HR51.03, P < 0.001), the risk of a claim for fracture was 2% higher (HR51.02, P < 0.001), and the risk of a claim for cataracts was 2% higher (HR51.02, P < 0.001). CONCLUSIONS: In asthmatics, greater cumulative OCS exposure is associated with statistically significant increased risks of osteoporosis, fracture and cataracts.
279
Onset and Duration of Action of Mometasone Inhalation Powder Measured by Impulse Oscillometry (IOS) K. Badampudi, S. Spector; California Allergy & Asthma Medical Group, Los Angeles, CA. RATIONALE: IOS is a noninvasive, unobtrusive alternative to spirometry in assessing airway impairment. IOS was measured in 21 asthmatics at intervals during a 4 week period with repeated mometasone dosing in order to determine the onset and duration of action as measured by IOS versus spirometry. METHODS: Either 220 mcg or 440 mcg MIP was given for 28-36 days in steroid-na€ıve adult asthmatics. The primary variable was low frequency reactance (AX) measured by the IOS. The secondary variable was forced expiratory volume in one second (FEV1) measured by spirometry. IOS testing was done at baseline and 30, 60, 90, 120, and 300 min after mometasone. Spirometry was done at 120 and 300 min. Patients returned for IOS and spirometry testing on the next 2 mornings and then weekly for 4 weeks. RESULTS: 21 patients were randomized to either 440 mcg or 220 mcg with the former group doing best. Significant decrease in AX was observed from baseline at 60 and 120 minutes Day 1 and on Days 2 and 3, and Weeks 1, 3 and 4. A significant increase in FEV1 was observed starting at Week 1 and continued over the 4 weeks of treatment. CONCLUSIONS: Improved airway function is seen earlier with IOS versus spirometry. The effect was maintained as the treatment continued. These early changes are consistent with what is seen with bronchial vasoconstriction.
J ALLERGY CLIN IMMUNOL FEBRUARY 2012
280
Association Between The STIP1 Polymorphism And The Response To Inhaled Steroid In Children With Asthma J. Hong1, M. Kang2, H. Kim3, J. Seo3, Y. Kim2, J. Yu3, S. Hong3; 1Cushing Academy, Ashburnham, MA, 2Asan Institue for Life Science, Asan Medical Center, Seoul, REPUBLIC OF KOREA, 3Childhood Asthma Atopy Center, Department of Pediatrics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, REPUBLIC OF KOREA. RATIONALE: Bronchial hyperresponsiveness is usually measured by bronchial challenges using direct stimuli by methacholine or indirect stimuli by adenosine 5’-monophosphate (AMP). Airway inflammation is more closely reflected by AMP challenge test. The stress-induced-phosphoprotein 1 (STIP1) is one of the genes in steroid pathway. And polymorphisms in STIP1 are correlated with lung function after corticosteroid treatment in white subjects. We investigated whether polymorphism (rs4980524) of the STIP1 was associated with clinical phenotypes and responsiveness to inhaled steroid in Korean asthmatic children. METHODS: We enrolled 84 asthmatic children. We prescribed budesonide (PulmicortÒ) turbuhaler 800ug/day for 8 weeks, and analyzed the responsiveness by AMP challenge test at 4 weeks after treatment and methacholine challenge test at 8 weeks after treatment. AMP and methacholine challenge test, spirometry and blood test for total IgE and eosinophil (total count, percent in white blood cells) were conducted. Polymorphism was genotyped by TaqMan assay. Subjects showing more or equal PC20 than baseline before treatment were defined as ‘good’. RESULTS: There were 70 good responders and 14 poor responders. When we analyzed characteristics of subjects, there were not significant differences between good and poor responder. And there was no association between the STIP1 polymorphism and steroid response by AMP or Methacholine challenge. CONCLUSION: The polymorphism (rs4980524) of STIP1 may be not a good predictor for responsiveness to inhaled steroid therapy in Korean children with asthma.
281
The Ability and Predictive Factors of Preschool Children to Use Swinghaler Device P. Lertchanaruengrith, P. Rattanasukol, N. Suratannon, N. Voraphani, P. Chatchatee, J. Ngamphaiboon; Division of Allergy and Immunology, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, THAILAND. RATIONALE: The type of inhaler device affects adherence to asthma medication. DPI is a device which does not require hand-lung coordination but has limited data in preschool populations. Swinghaler required low peak inspiratory flow rate (PIFR). We examined the ability to use Swinghaler in preschool children compared to Turbuhaler and the predictive factors for the use of device effectively. METHODS: One hundred and eighty healthy children, aged 3-6 years, were included. Swinghaler tester and Turbutester were used. The PIFR was measured by In-Check Dial after they were trained. RESULTS: The ability to use Swinghaler and Turbuhaler in children aged 3-4, 4-5, and 5-6 years was 72.2%, 80.7%, 84.8% and 48.9%, 61.4% and 78.8% respectively. The ability to use Swinghaler in children aged 3-4 and 4-5 years was significantly higher than that of Turbuhaler (p < 0.001 and p 5 0.003, respectively). Eighty-six of 103 children (83.5%) aged 4 years or older and 108 of 132 children (81.8%) with height more than 100 centimeters can use Swinghaler (p 5 0.02 and p 5 0.015, respectively). Mean PIFR in children aged 3-4, 4-5, and 5-6 years was 35.2613.1, 41.3614.6, and 48.7616.4 L/min, respectively. Factors which independently associated with PIFR were male gender and height (p 5 0.01 and p < 0.001, respectively). CONCLUSIONS: Children from the age of 4 years or a height from 110 centimeters were able to generate adequate PIFR to use the Swinghaler. This device can be considered as an alternative inhaler device to MDI for the well-trained preschool children.
278
SUNDAY
Oral Corticosteroid Use Increases the Risk of Glucocorticoidrelated Adverse Events in Asthmatics J. L. Zazzali1, M. Broder2, E. Chang2; 1Genentech, Inc., South San Francisco, CA, 2Partnership for Health Analytic Research, Beverly Hills, CA. RATIONALE: Oral corticosteroids (OCS) are a mainstay of asthma therapy for managing severe symptoms and exacerbations. Prolonged systemic exposure to glucocorticoids is known to be associated with increased risk of glucocorticoid-related adverse events (GAEs). Our objective was to determine the risk of GAEs associated with cumulative OCS exposure in asthmatics. METHODS: Retrospective cohort analysis of adult asthmatics using a HIPAA-compliant claims database. Patients were continuously enrolled during 2002-2003 and were followed until the end of enrollment or study end (2007) whichever was earlier (median5 1,461 days observation). Patients with potential GAEs in the first year were excluded. Cox regression models estimated adjusted hazard ratios of the risk of GAEs (osteoporosis, fracture and cataracts) for different OCS exposure levels, measured by cumulative prednisone-equivalent dose as recorded on pharmacy claims, while adjusting for age, gender, region, usual care physician specialty, and chronic conditions. RESULTS: We examined 37,891 asthmatics (mean age544.9 years, 65.7% female). For every 1,000 mg increase in prednisone-equivalent OCS exposure, the risk of a claim for osteoporosis was 3% higher (HR51.03, P < 0.001), the risk of a claim for fracture was 2% higher (HR51.02, P < 0.001), and the risk of a claim for cataracts was 2% higher (HR51.02, P < 0.001). CONCLUSIONS: In asthmatics, greater cumulative OCS exposure is associated with statistically significant increased risks of osteoporosis, fracture and cataracts.
279
Onset and Duration of Action of Mometasone Inhalation Powder Measured by Impulse Oscillometry (IOS) K. Badampudi, S. Spector; California Allergy & Asthma Medical Group, Los Angeles, CA. RATIONALE: IOS is a noninvasive, unobtrusive alternative to spirometry in assessing airway impairment. IOS was measured in 21 asthmatics at intervals during a 4 week period with repeated mometasone dosing in order to determine the onset and duration of action as measured by IOS versus spirometry. METHODS: Either 220 mcg or 440 mcg MIP was given for 28-36 days in steroid-na€ıve adult asthmatics. The primary variable was low frequency reactance (AX) measured by the IOS. The secondary variable was forced expiratory volume in one second (FEV1) measured by spirometry. IOS testing was done at baseline and 30, 60, 90, 120, and 300 min after mometasone. Spirometry was done at 120 and 300 min. Patients returned for IOS and spirometry testing on the next 2 mornings and then weekly for 4 weeks. RESULTS: 21 patients were randomized to either 440 mcg or 220 mcg with the former group doing best. Significant decrease in AX was observed from baseline at 60 and 120 minutes Day 1 and on Days 2 and 3, and Weeks 1, 3 and 4. A significant increase in FEV1 was observed starting at Week 1 and continued over the 4 weeks of treatment. CONCLUSIONS: Improved airway function is seen earlier with IOS versus spirometry. The effect was maintained as the treatment continued. These early changes are consistent with what is seen with bronchial vasoconstriction.
J ALLERGY CLIN IMMUNOL FEBRUARY 2012
280
Association Between The STIP1 Polymorphism And The Response To Inhaled Steroid In Children With Asthma J. Hong1, M. Kang2, H. Kim3, J. Seo3, Y. Kim2, J. Yu3, S. Hong3; 1Cushing Academy, Ashburnham, MA, 2Asan Institue for Life Science, Asan Medical Center, Seoul, REPUBLIC OF KOREA, 3Childhood Asthma Atopy Center, Department of Pediatrics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, REPUBLIC OF KOREA. RATIONALE: Bronchial hyperresponsiveness is usually measured by bronchial challenges using direct stimuli by methacholine or indirect stimuli by adenosine 5’-monophosphate (AMP). Airway inflammation is more closely reflected by AMP challenge test. The stress-induced-phosphoprotein 1 (STIP1) is one of the genes in steroid pathway. And polymorphisms in STIP1 are correlated with lung function after corticosteroid treatment in white subjects. We investigated whether polymorphism (rs4980524) of the STIP1 was associated with clinical phenotypes and responsiveness to inhaled steroid in Korean asthmatic children. METHODS: We enrolled 84 asthmatic children. We prescribed budesonide (PulmicortÒ) turbuhaler 800ug/day for 8 weeks, and analyzed the responsiveness by AMP challenge test at 4 weeks after treatment and methacholine challenge test at 8 weeks after treatment. AMP and methacholine challenge test, spirometry and blood test for total IgE and eosinophil (total count, percent in white blood cells) were conducted. Polymorphism was genotyped by TaqMan assay. Subjects showing more or equal PC20 than baseline before treatment were defined as ‘good’. RESULTS: There were 70 good responders and 14 poor responders. When we analyzed characteristics of subjects, there were not significant differences between good and poor responder. And there was no association between the STIP1 polymorphism and steroid response by AMP or Methacholine challenge. CONCLUSION: The polymorphism (rs4980524) of STIP1 may be not a good predictor for responsiveness to inhaled steroid therapy in Korean children with asthma.
281
The Ability and Predictive Factors of Preschool Children to Use Swinghaler Device P. Lertchanaruengrith, P. Rattanasukol, N. Suratannon, N. Voraphani, P. Chatchatee, J. Ngamphaiboon; Division of Allergy and Immunology, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, THAILAND. RATIONALE: The type of inhaler device affects adherence to asthma medication. DPI is a device which does not require hand-lung coordination but has limited data in preschool populations. Swinghaler required low peak inspiratory flow rate (PIFR). We examined the ability to use Swinghaler in preschool children compared to Turbuhaler and the predictive factors for the use of device effectively. METHODS: One hundred and eighty healthy children, aged 3-6 years, were included. Swinghaler tester and Turbutester were used. The PIFR was measured by In-Check Dial after they were trained. RESULTS: The ability to use Swinghaler and Turbuhaler in children aged 3-4, 4-5, and 5-6 years was 72.2%, 80.7%, 84.8% and 48.9%, 61.4% and 78.8% respectively. The ability to use Swinghaler in children aged 3-4 and 4-5 years was significantly higher than that of Turbuhaler (p < 0.001 and p 5 0.003, respectively). Eighty-six of 103 children (83.5%) aged 4 years or older and 108 of 132 children (81.8%) with height more than 100 centimeters can use Swinghaler (p 5 0.02 and p 5 0.015, respectively). Mean PIFR in children aged 3-4, 4-5, and 5-6 years was 35.2613.1, 41.3614.6, and 48.7616.4 L/min, respectively. Factors which independently associated with PIFR were male gender and height (p 5 0.01 and p < 0.001, respectively). CONCLUSIONS: Children from the age of 4 years or a height from 110 centimeters were able to generate adequate PIFR to use the Swinghaler. This device can be considered as an alternative inhaler device to MDI for the well-trained preschool children.