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Observing Medical Insurance Claims Data in a High Risk Asthma Population and Targeting Behavioral Patterns to Improve Controller Medication Compliance and Reduce Emergency Department Visits
Abstracts AB243
J ALLERGY CLIN IMMUNOL VOLUME 135, NUMBER 2
Observing Medical Insurance Claims Data in a High Risk Asthma Population and Targeting Behavioral Patterns to Improve Controller Medication Compliance and Reduce Emergency Department Visits Sweeti Bhakta-Jain, MD1, Christie F. Michael, MD2, Christina Underhill, PhD3; 1UTHSC Department of Pediatrics, Memphis, TN, 2University of Tennessee Division of Clinical Immunology, Memphis, TN, 3LeBonheur Childrens Hospital, Division of Community Health and Well-Being. RATIONALE: We hypothesize that patients are more likely to refill a controller medication following an outpatient office visit or hospitalization. METHODS: Tenncare claims data was analyzed in a high risk asthma population from 2011-2013. An observational study was performed involving 354 patients ages 2-18. Number of controller medication refills in association with outpatient office visits was compared to the number of controller medication refills without clinical outpatient encounters. RESULTS: Patients were more likely to refill controller medication following an outpatient visit or hospitalization than emergency department visit. Patients who had more frequent asthma outpatient visits were found to have less emergency room visits on average. CONCLUSIONS: This data suggests that in a high risk asthma population, increasing the number of asthma clinic visits improves compliance of controller medication and decreases emergency room visits.
785
Relationship of S100A9 (S100 Calcium binding Protein A9) with Neutophilic Inflammation in Murine Asthma Model Jong-Sook Park, MD, Tae-Hyeong Lee, PhD student, Hye-Rim Shin, MS, Hyun Ji Song, MS, Jeong-Dong Kim, MS, Choon-Sik Park, MD; Soonchunhyang University Bucheon Hospital, Bucheon, South Korea. RATIONALE: We previously published elevation of S100A9 protein in sputum of neutrophilic severe uncontrolled asthmatics compared with stable asthmatics. [Annels of allergy, asthma, immunology on 2013 Oct;111(4):268-275] suggesting possible role of S100A9 in neutrophilic severe asthma. The aim of this study was to validate the temporal relationship of S100A9 with neutrophilic airway inflammation and inflammasome activation in CFA/OVA-sensitized/challenged murine asthma model. METHODS: Expression of S100A9, S100A8 mRNA and protein levels and activated caspase-1 were measured using a RT-PCR, Real-time PCR and western blot. Spatial expression of S100A9 protein was visualized by Immunohistochemical stain and Immunofluorescene stain. To evaluate the potency of S100A9 on neutrophilic inflammation and activation of inflammsome, temporal changes of neutrophil infiltration and activation of caspase-1 were analyzed in lung tissues of the CFA/OVA model and in those of C57BL/6 mice after intratracheal S100A9 protein. RESULTS: S100A9 and P20 - activated caspase-1 concomitantly started to increase from day 14 and peaked at day 23 while the number of total cells, macrophage and neutrophils significantly increased with concomitant increase of Penh at day 23. Neutrophil elastase and S100A9 were colocalized in peri-bronchially infiltrating cells and apical portion of bronchial epithelium. Intratracheal instillation of S100A9 (10ug) induced rapid increase of neutrophils in BAL fluid from 2 hr, peaked at 8 hr, then progressively decreased till 80 hr with concomitant activation of caspase-1. CONCLUSIONS: S100A9 protein and activated caspase-1 begin to express earlier than the appearance of neutrophilics in the airway of neutrophilic inflammation model and S100A9 directly activate inflammasome in the airway.
786
The Contribution of Peptide-MHC Affinity to the Efficacy of Peptide Immunotherapy in a Murine Model of Allergic Airways Disease Daniel M. Moldaver1,2, Tarandeep Singh1,2, Melissa Babra1,2, Christopher Rudulier1, Mantej S. Bharhani1,2, Jennifer Wattie1,2, Marianne van Hage, MD, PhD3, Mark D. Inman, MD, PhD1,2, Mark Larche, PhD1,2; 1McMaster University, Hamilton, ON, Canada, 2Firestone Institute for Respiratory Health, Hamilton, ON, Canada, 3Karolinska Institutet, Department of Medicina Solna, Clinical Immunology and Allergy Unit, Stockholm, Sweden. RATIONALE: In order to be effective at the population level, peptide immunotherapy (PIT) preparations commonly contain several allergenderived peptides; chosen by their ability to promiscuously bind several Major Histocompatibility Complex (MHC) molecules. Since promiscuous peptides may bind with differing affinity to individual MHC molecules, we sought to understand whether peptide-MHC affinity controls the degree of tolerance elicited, in a humanized murine model of allergic airways disease. METHODS: Female HLA-DR4 transgenic mice (Taconic Farms;6wks, n55/group,two independent experiments) were sensitized to cat allergens via intraperitoneal injections of Fel d 1 in alum and subsequent intranasal instillations of cat dander extract (CDE). Mice were treated with one of seven peptides, intradermally. Treatment peptides varied in affinity and were assessed individually at several concentrations (ranging from 0.01 to 100 mg). Control mice received sham treatment, or an irrelevant peptide (HA(306-318)). Following therapy mice were challenged intranasally with CDE and 48-hours later airway inflammation and responsiveness were assessed by histology and a methacholine challenge, respectively. _1mg) treatment with high affinity peptides RESULTS: Low dose (< significantly ameliorated airway hyperresponsiveness (AHR), and eosinophilic infiltration (p < 0.05, one-way ANOVA & t-test). Moderate affinity _1mg) to suppress eosinophilic accumupeptides required higher dosing (> lation, and were unable to consistently suppress AHR. Sham, irrelevant and low affinity peptide treated mice were not protected from eosinophilia or AHR. CONCLUSIONS: Both high affinity and moderate affinity peptides elicited antigen-specific tolerance, but at different doses. Clinical response to peptide immunotherapy may vary between individuals as a function of both MHC haplotype and peptide dose.
TUESDAY
784
J ALLERGY CLIN IMMUNOL VOLUME 135, NUMBER 2
Observing Medical Insurance Claims Data in a High Risk Asthma Population and Targeting Behavioral Patterns to Improve Controller Medication Compliance and Reduce Emergency Department Visits Sweeti Bhakta-Jain, MD1, Christie F. Michael, MD2, Christina Underhill, PhD3; 1UTHSC Department of Pediatrics, Memphis, TN, 2University of Tennessee Division of Clinical Immunology, Memphis, TN, 3LeBonheur Childrens Hospital, Division of Community Health and Well-Being. RATIONALE: We hypothesize that patients are more likely to refill a controller medication following an outpatient office visit or hospitalization. METHODS: Tenncare claims data was analyzed in a high risk asthma population from 2011-2013. An observational study was performed involving 354 patients ages 2-18. Number of controller medication refills in association with outpatient office visits was compared to the number of controller medication refills without clinical outpatient encounters. RESULTS: Patients were more likely to refill controller medication following an outpatient visit or hospitalization than emergency department visit. Patients who had more frequent asthma outpatient visits were found to have less emergency room visits on average. CONCLUSIONS: This data suggests that in a high risk asthma population, increasing the number of asthma clinic visits improves compliance of controller medication and decreases emergency room visits.
785
Relationship of S100A9 (S100 Calcium binding Protein A9) with Neutophilic Inflammation in Murine Asthma Model Jong-Sook Park, MD, Tae-Hyeong Lee, PhD student, Hye-Rim Shin, MS, Hyun Ji Song, MS, Jeong-Dong Kim, MS, Choon-Sik Park, MD; Soonchunhyang University Bucheon Hospital, Bucheon, South Korea. RATIONALE: We previously published elevation of S100A9 protein in sputum of neutrophilic severe uncontrolled asthmatics compared with stable asthmatics. [Annels of allergy, asthma, immunology on 2013 Oct;111(4):268-275] suggesting possible role of S100A9 in neutrophilic severe asthma. The aim of this study was to validate the temporal relationship of S100A9 with neutrophilic airway inflammation and inflammasome activation in CFA/OVA-sensitized/challenged murine asthma model. METHODS: Expression of S100A9, S100A8 mRNA and protein levels and activated caspase-1 were measured using a RT-PCR, Real-time PCR and western blot. Spatial expression of S100A9 protein was visualized by Immunohistochemical stain and Immunofluorescene stain. To evaluate the potency of S100A9 on neutrophilic inflammation and activation of inflammsome, temporal changes of neutrophil infiltration and activation of caspase-1 were analyzed in lung tissues of the CFA/OVA model and in those of C57BL/6 mice after intratracheal S100A9 protein. RESULTS: S100A9 and P20 - activated caspase-1 concomitantly started to increase from day 14 and peaked at day 23 while the number of total cells, macrophage and neutrophils significantly increased with concomitant increase of Penh at day 23. Neutrophil elastase and S100A9 were colocalized in peri-bronchially infiltrating cells and apical portion of bronchial epithelium. Intratracheal instillation of S100A9 (10ug) induced rapid increase of neutrophils in BAL fluid from 2 hr, peaked at 8 hr, then progressively decreased till 80 hr with concomitant activation of caspase-1. CONCLUSIONS: S100A9 protein and activated caspase-1 begin to express earlier than the appearance of neutrophilics in the airway of neutrophilic inflammation model and S100A9 directly activate inflammasome in the airway.
786
The Contribution of Peptide-MHC Affinity to the Efficacy of Peptide Immunotherapy in a Murine Model of Allergic Airways Disease Daniel M. Moldaver1,2, Tarandeep Singh1,2, Melissa Babra1,2, Christopher Rudulier1, Mantej S. Bharhani1,2, Jennifer Wattie1,2, Marianne van Hage, MD, PhD3, Mark D. Inman, MD, PhD1,2, Mark Larche, PhD1,2; 1McMaster University, Hamilton, ON, Canada, 2Firestone Institute for Respiratory Health, Hamilton, ON, Canada, 3Karolinska Institutet, Department of Medicina Solna, Clinical Immunology and Allergy Unit, Stockholm, Sweden. RATIONALE: In order to be effective at the population level, peptide immunotherapy (PIT) preparations commonly contain several allergenderived peptides; chosen by their ability to promiscuously bind several Major Histocompatibility Complex (MHC) molecules. Since promiscuous peptides may bind with differing affinity to individual MHC molecules, we sought to understand whether peptide-MHC affinity controls the degree of tolerance elicited, in a humanized murine model of allergic airways disease. METHODS: Female HLA-DR4 transgenic mice (Taconic Farms;6wks, n55/group,two independent experiments) were sensitized to cat allergens via intraperitoneal injections of Fel d 1 in alum and subsequent intranasal instillations of cat dander extract (CDE). Mice were treated with one of seven peptides, intradermally. Treatment peptides varied in affinity and were assessed individually at several concentrations (ranging from 0.01 to 100 mg). Control mice received sham treatment, or an irrelevant peptide (HA(306-318)). Following therapy mice were challenged intranasally with CDE and 48-hours later airway inflammation and responsiveness were assessed by histology and a methacholine challenge, respectively. _1mg) treatment with high affinity peptides RESULTS: Low dose (< significantly ameliorated airway hyperresponsiveness (AHR), and eosinophilic infiltration (p < 0.05, one-way ANOVA & t-test). Moderate affinity _1mg) to suppress eosinophilic accumupeptides required higher dosing (> lation, and were unable to consistently suppress AHR. Sham, irrelevant and low affinity peptide treated mice were not protected from eosinophilia or AHR. CONCLUSIONS: Both high affinity and moderate affinity peptides elicited antigen-specific tolerance, but at different doses. Clinical response to peptide immunotherapy may vary between individuals as a function of both MHC haplotype and peptide dose.
TUESDAY
784