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Levels of Plasma Complement Split Products C3a desArg and C5a desArg and their Peripheral Blood Receptors are Elevated in Outpatient Adult Asthmatics with Decreased Asthma Control as Determined by the ACT and ATAQ Questionnaires
S84 Abstracts
311
SUNDAY
Levels of Plasma Complement Split Products C3a desArg and C5a desArg and their Peripheral Blood Receptors are Elevated in Outpatient Adult Asthmatics with Decreased Asthma Control as Determined by the ACT and ATAQ Questionnaires R. Shams, D. P. Erstein, M. S. Dzhindzhikhashvili, F. Hajee, S. Chice, M. Nowakowski, H. G. Durkin, R. Joks; Center for Allergy and Asthma Research at SUNY Downstate Medical Center, Brooklyn, NY. RATIONALE: The recent NAEPP EPR-3 asthma guidelines emphasize the measurement of impairment from asthma and suggest the regular use of two validated questionnaires, the ACT (Asthma Control Test) and the ATAQ (Asthma Therapy Assessment Questionnaire) to determine the degree of control of asthma. As we have previously shown levels of the complement split product (CSP) plasma C5a desArg correlate with asthma quality of life scores (AQLQ, Juniper)(Charlot, 2005), we determined whether C5a desArg or C3a desArg and their peripheral blood receptor levels (CSPr) correlate with asthma control in adult asthmatics seen in an outpatient setting. METHODS: During a single study visit plasma and peripheral blood cellular receptor levels of C5a desArg and C3a desArg, and total serum IgE (ELISA, flow cytometry, and fluorescence enzyme immunoassay) were obtained from adult patients with allergic asthma (n 5 14), allergic rhinoconjunctivitis (n 5 4), or controls (n 5 4). After completing the ACT and ATAQ questionnaires, subjects underwent measurement of exhaled nitric oxide (Niox Mino) and spirometry. RESULTS: Increased levels of plasma C3a desArg and its lymphocyte receptor (LC3aR) correlate with decreased asthma control as measured by the ATAQ (p 5 0.04 for both). The correlation of monocyte C3aR levels with ATAQ, C5a-desArg levels with ACT score, and lymphocyte C5aR level CD88) with ATAQ all approached significance (p 5 0.08, 0.06, and 0.06, respectively). CONCLUSIONS: Taken together, our findings suggest that both CSP and CSPr levels correlate with both asthma quality of life and asthma control and there is a degree of increased systemic inflammation involving complement in patients with poorly controlled asthma.
312
Salivary Analyte Profiles and Asthma Severity P. J. Wexler1, W. L. Siqueira2, E. J. Helmerhorst2, F. G. Oppenheim2, R. Lomasky3, C. E. Brodley3, R. B. Hayman4, T. M. Blicharz4, D. R. Walt4, F. F. Little1; 1Pulmonary Center, Boston University School of Medicine, Boston, MA, 2Boston University Goldman School of Dental Medicine, Boston, MA, 3Department of Computer Science, Tufts University, Medford, MA, 4Department of Chemistry, Tufts University, Medford, MA. RATIONALE: There are similarities in the upper (sinus, nasal) and lower (bronchial) airway inflammatory response. Due to its direct anatomic relation with the mouth, we hypothesize that salivary cytokine and chemokine concentrations reflect the inflammatory composition of the airways. The measurement of selected analytes in saliva could provide biomarkers of asthma control. METHODS: A convenience sample of asthmatics in various stages of severity and control were recruited from the B.U. Asthma/Allergy Clinic. In addition to usual care, subjects completed a comprehensive questionnaire and focused oral exam. Asthma control and severity were determined based on the 2006 GINA and 2002 EPR-2 update guidelines. Supernatant from whole saliva was isolated and a panel of 10 inflammatory markers measured using a microsphere-based antibody array. Decision analysis was performed using C4.5 algorithm and support vector machines. RESULTS: One hundred seventy five asthmatics representing 227 subject visits were recruited, of which 68% had moderate or severe asthma, 83% had coexistent allergic rhinitis, and 16% were in exacerbation. Of the 10 inflammatory mediators queried in 107 samples, salivary IL-8, MCP-1, and EGF predicted asthma severity with 75% confidence. CONCLUSIONS: Candidate biomarkers of airway inflammation can be rapidly measured in a multiplex fashion in whole saliva and a profile can be created to predict asthma severity. In the future, this profile will be
J ALLERGY CLIN IMMUNOL FEBRUARY 2009
correlated with asthma control and may be a tool to aid clinical asthma management.
313
HMG-CoA Reductase Inhibitors and Asthma Severity S. C. Christiansen1,2, M. Schatz1, J. Eddleston2,3, A. Wagelie3 Steffen , S. J. Yang1, W. Chen1, B. L. Zuraw2,3; 1Southern CA Permanente Med Grp, San Diego, CA, 2University of California, San Diego, CA, 3Veterans Affairs Medical Center, San Diego, CA. RATIONALE: Since HMG-CoA reductase inhibitors (statins) have been shown to exert anti-inflammatory effects, we investigated the relationship between statin usage and asthma severity. METHODS: Asthmatic subjects 18 years old were identified in the Kaiser Permanente database. Stain exposed and control patients were matched for baseline short-acting beta agonist (SABA) use. Outcomes (SABA use, asthma hospitalizations emergency department [ED] visits, and oral corticosteroid dispensings) were compared for the year before and the year after initiation of statin therapy (or a similar index date in controls). Analyses were adjusted for age, sex, baseline severity, and comorbidities. RESULTS: 7783 asthmatic subjects with statin usage and 35,375 asthmatic controls were included for analysis. Diabetes and reflux were more common in the statin group (31% vs 5% and 22% vs 16% respectively). Although matched for SABA use, the statin group had more corticosteroids dispensed, ED visits and hospitalizations during the index year than the control group. Statin therapy did not narrow these discrepancies: risk ratios for the statin versus control group in the year following initiation of statins were 1.76 for weighted SABA use, 2.30 for SABA use >6, 1.20 for ED visits, 1.17 for hospitalization and 1.41 for oral corticosteroid dispensing. While not an outcome parameter, controller therapy was greater for the statin group and did not significantly change in the follow-up year. CONCLUSIONS: Asthmatic subjects selected for statin use appear to have inherently more severe disease and asthma morbidity vs non treated asthmatic counterparts, a difference that was not corrected by statin use.
314
Immunological Analysis of the Atopic March (AM) J. Spergel1,2, M. Boguniewicz3, J. Orange1,2, K. Pinzone1, R. Harbeck3, S. B. Leung3, D. Y. Leung3; 1The Children’s Hospital of Philadelphia, Philadelphia, PA, 2Univ. of Pennsylvania School of Medicine, Philadelphia, PA, 3National Jewish Health, Denver, CO. RATIONALE: To examine the immunologic phenotype of 104 children with atopic dermatitis (AD) during the development of asthma and allergies. METHODS: 104 children ages 3-18 months with AD were enrolled within 3 months of AD diagnosis in a 6-year prospective trial of the AM. At 18, 30 and 42 months, total and specific IgE, and lymphocyte phenotype were measured. Lymphoproliferation assay (LPA) and cytokine production to birch, Der p1, Fel d1, tetanus and PHA were compared. RESULTS: 56 children progressed in the AM to develop food allergy, asthma, allergic rhinitis or allergic conjunctivitis compared to 48 patients who did not progress (non-AM (NAM). The AM population had significantly greater total IgE (AM-693 kU/ml, NAM-55 kU/ml), more severe eczema only at 42 months (EASI score-2.95, NAM-0.34, p < 0.01), more positive specific IgE (sIgE) to allergens (# of positive sIgE 3.84-AM, 1.64-NAM, p < 0.01) and positive LPA (stimulation index > 3 or 5) to the allergens than the non-AM group at all time points with significant p value (p < 0.05) for years 1 and 2. The AM population also had a higher expression of CLA- (IL4 and IL5) T cells at 18 month (p < 0.04), 30 months (p < 0.15) and 42 months (p < 0.15). CONCLUSIONS: These results suggest that Th2 CLA-T cells in the peripheral blood serves as a marker of the atopic march.
311
SUNDAY
Levels of Plasma Complement Split Products C3a desArg and C5a desArg and their Peripheral Blood Receptors are Elevated in Outpatient Adult Asthmatics with Decreased Asthma Control as Determined by the ACT and ATAQ Questionnaires R. Shams, D. P. Erstein, M. S. Dzhindzhikhashvili, F. Hajee, S. Chice, M. Nowakowski, H. G. Durkin, R. Joks; Center for Allergy and Asthma Research at SUNY Downstate Medical Center, Brooklyn, NY. RATIONALE: The recent NAEPP EPR-3 asthma guidelines emphasize the measurement of impairment from asthma and suggest the regular use of two validated questionnaires, the ACT (Asthma Control Test) and the ATAQ (Asthma Therapy Assessment Questionnaire) to determine the degree of control of asthma. As we have previously shown levels of the complement split product (CSP) plasma C5a desArg correlate with asthma quality of life scores (AQLQ, Juniper)(Charlot, 2005), we determined whether C5a desArg or C3a desArg and their peripheral blood receptor levels (CSPr) correlate with asthma control in adult asthmatics seen in an outpatient setting. METHODS: During a single study visit plasma and peripheral blood cellular receptor levels of C5a desArg and C3a desArg, and total serum IgE (ELISA, flow cytometry, and fluorescence enzyme immunoassay) were obtained from adult patients with allergic asthma (n 5 14), allergic rhinoconjunctivitis (n 5 4), or controls (n 5 4). After completing the ACT and ATAQ questionnaires, subjects underwent measurement of exhaled nitric oxide (Niox Mino) and spirometry. RESULTS: Increased levels of plasma C3a desArg and its lymphocyte receptor (LC3aR) correlate with decreased asthma control as measured by the ATAQ (p 5 0.04 for both). The correlation of monocyte C3aR levels with ATAQ, C5a-desArg levels with ACT score, and lymphocyte C5aR level CD88) with ATAQ all approached significance (p 5 0.08, 0.06, and 0.06, respectively). CONCLUSIONS: Taken together, our findings suggest that both CSP and CSPr levels correlate with both asthma quality of life and asthma control and there is a degree of increased systemic inflammation involving complement in patients with poorly controlled asthma.
312
Salivary Analyte Profiles and Asthma Severity P. J. Wexler1, W. L. Siqueira2, E. J. Helmerhorst2, F. G. Oppenheim2, R. Lomasky3, C. E. Brodley3, R. B. Hayman4, T. M. Blicharz4, D. R. Walt4, F. F. Little1; 1Pulmonary Center, Boston University School of Medicine, Boston, MA, 2Boston University Goldman School of Dental Medicine, Boston, MA, 3Department of Computer Science, Tufts University, Medford, MA, 4Department of Chemistry, Tufts University, Medford, MA. RATIONALE: There are similarities in the upper (sinus, nasal) and lower (bronchial) airway inflammatory response. Due to its direct anatomic relation with the mouth, we hypothesize that salivary cytokine and chemokine concentrations reflect the inflammatory composition of the airways. The measurement of selected analytes in saliva could provide biomarkers of asthma control. METHODS: A convenience sample of asthmatics in various stages of severity and control were recruited from the B.U. Asthma/Allergy Clinic. In addition to usual care, subjects completed a comprehensive questionnaire and focused oral exam. Asthma control and severity were determined based on the 2006 GINA and 2002 EPR-2 update guidelines. Supernatant from whole saliva was isolated and a panel of 10 inflammatory markers measured using a microsphere-based antibody array. Decision analysis was performed using C4.5 algorithm and support vector machines. RESULTS: One hundred seventy five asthmatics representing 227 subject visits were recruited, of which 68% had moderate or severe asthma, 83% had coexistent allergic rhinitis, and 16% were in exacerbation. Of the 10 inflammatory mediators queried in 107 samples, salivary IL-8, MCP-1, and EGF predicted asthma severity with 75% confidence. CONCLUSIONS: Candidate biomarkers of airway inflammation can be rapidly measured in a multiplex fashion in whole saliva and a profile can be created to predict asthma severity. In the future, this profile will be
J ALLERGY CLIN IMMUNOL FEBRUARY 2009
correlated with asthma control and may be a tool to aid clinical asthma management.
313
HMG-CoA Reductase Inhibitors and Asthma Severity S. C. Christiansen1,2, M. Schatz1, J. Eddleston2,3, A. Wagelie3 Steffen , S. J. Yang1, W. Chen1, B. L. Zuraw2,3; 1Southern CA Permanente Med Grp, San Diego, CA, 2University of California, San Diego, CA, 3Veterans Affairs Medical Center, San Diego, CA. RATIONALE: Since HMG-CoA reductase inhibitors (statins) have been shown to exert anti-inflammatory effects, we investigated the relationship between statin usage and asthma severity. METHODS: Asthmatic subjects 18 years old were identified in the Kaiser Permanente database. Stain exposed and control patients were matched for baseline short-acting beta agonist (SABA) use. Outcomes (SABA use, asthma hospitalizations emergency department [ED] visits, and oral corticosteroid dispensings) were compared for the year before and the year after initiation of statin therapy (or a similar index date in controls). Analyses were adjusted for age, sex, baseline severity, and comorbidities. RESULTS: 7783 asthmatic subjects with statin usage and 35,375 asthmatic controls were included for analysis. Diabetes and reflux were more common in the statin group (31% vs 5% and 22% vs 16% respectively). Although matched for SABA use, the statin group had more corticosteroids dispensed, ED visits and hospitalizations during the index year than the control group. Statin therapy did not narrow these discrepancies: risk ratios for the statin versus control group in the year following initiation of statins were 1.76 for weighted SABA use, 2.30 for SABA use >6, 1.20 for ED visits, 1.17 for hospitalization and 1.41 for oral corticosteroid dispensing. While not an outcome parameter, controller therapy was greater for the statin group and did not significantly change in the follow-up year. CONCLUSIONS: Asthmatic subjects selected for statin use appear to have inherently more severe disease and asthma morbidity vs non treated asthmatic counterparts, a difference that was not corrected by statin use.
314
Immunological Analysis of the Atopic March (AM) J. Spergel1,2, M. Boguniewicz3, J. Orange1,2, K. Pinzone1, R. Harbeck3, S. B. Leung3, D. Y. Leung3; 1The Children’s Hospital of Philadelphia, Philadelphia, PA, 2Univ. of Pennsylvania School of Medicine, Philadelphia, PA, 3National Jewish Health, Denver, CO. RATIONALE: To examine the immunologic phenotype of 104 children with atopic dermatitis (AD) during the development of asthma and allergies. METHODS: 104 children ages 3-18 months with AD were enrolled within 3 months of AD diagnosis in a 6-year prospective trial of the AM. At 18, 30 and 42 months, total and specific IgE, and lymphocyte phenotype were measured. Lymphoproliferation assay (LPA) and cytokine production to birch, Der p1, Fel d1, tetanus and PHA were compared. RESULTS: 56 children progressed in the AM to develop food allergy, asthma, allergic rhinitis or allergic conjunctivitis compared to 48 patients who did not progress (non-AM (NAM). The AM population had significantly greater total IgE (AM-693 kU/ml, NAM-55 kU/ml), more severe eczema only at 42 months (EASI score-2.95, NAM-0.34, p < 0.01), more positive specific IgE (sIgE) to allergens (# of positive sIgE 3.84-AM, 1.64-NAM, p < 0.01) and positive LPA (stimulation index > 3 or 5) to the allergens than the non-AM group at all time points with significant p value (p < 0.05) for years 1 and 2. The AM population also had a higher expression of CLA- (IL4 and IL5) T cells at 18 month (p < 0.04), 30 months (p < 0.15) and 42 months (p < 0.15). CONCLUSIONS: These results suggest that Th2 CLA-T cells in the peripheral blood serves as a marker of the atopic march.