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Magnetic Resonance Imaging (MRI) Technique Detects Differences in Lung Function in Boys and Girls who are at Risk for Asthma
502
Cultured Human Mast Cells are heterogeneous for expression of the High Affinity IgE Receptor FceRI H. Hoffmann1, P. Munk Frandsen1, L. Harder Christensen2, R. Dahl1, P. Schiøtz1; 1Aarhus University, Aarhus, DENMARK, 2ALK-Abello, Hørsholm, DENMARK. RATIONALE: Mast cells expressing the high affinity IgE receptor (FceRI) are a cornerstone of the type I allergic reaction. We present data from cultured human mast cells suggesting that this is only one subtype of mast cells. We studied the response of mast cells through FceRI and effect of stabilization of surface expression of FceRI by IgE. METHODS: Mast cells were cultured from CD1331 progenitors from peripheral (PBMC) or cord blood. FceRI was stabilized with 2mg/ml IgE for 2 days. IgE density was measured with QiFiKit. Cells were activated by addition of anti-FceRI antibody in log dilutions from 1ng-10mg/ml, and labeled with anti-CD63 and anti-CD203c. Maximal activation, sensitivity and co-operativity were determined from non-linear curves fitted to activation data. RESULTS: All cultures were homogeneous for tryptase and metachromasy. Only cells expressing FceRI, but all cells expressing FceRI, were activated. PBMC bind 203 000 molecules IgE/cell. All cells binding IgE can be activated by crosslinking of FceRI to upregulate CD63. Expression of CD203c and histamine release correlates with expression of CD63. Stabilization of FceRI with IgE doubled the number of CD631 activatable cells (p50.0001), increased sensitivity and slope factor of PBMC six-fold. Anti-IgE reversed this effect (p50.0002), but did not reduce activation levels below that of cell lines not stabilized with IgE. CONCLUSIONS: The fraction of PBMC that binds high levels of IgE can be activated through FceRI. Baseline expression of FceRI is independent of anti-IgE. The fraction of PBMC that does not express FceRI has a different phenotype.
503
Is Exhaled Nitric Oxide (FeNO) Elevated in Children with Acute Asthma? J. Malka, J. R. Fish, P. Pickering, P. Ramamoorthy, M. Gleason, J. D. Spahn; National Jewish Health, Denver, CO. RATIONALE: There is conflicting data regarding whether exhaled nitric oxide (FeNO) levels are elevated in children presenting with acute asthma. METHODS: We sought to prospectively determine if FeNO levels are differentially elevated in children with viral- vs. allergen-driven acute asthma. 82 children with acute asthma completed a questionnaire regarding symptoms, albuterol use and whether the illness was associated with a viral-infection or allergen exposure, as well as spirometry & FeNO before and after prednisone (2 mg/kg/d) for 5 to 7 days. All children had baseline spirometry, FeNO and aeroallergen skin testing. RESULTS: The mean age was 11.6 1/- 3.3 years, 59% were male and 86% atopic. Baseline FeNO was 22 ppb increasing to 40 ppb during the exacerbation. There was no difference in the decline in FEV1 (19.363.3 vs. 25.363.0; p50.2) FEV1/FVC (10 6 2.1 vs. 10 6 2.4; p50.86), duration of nocturnal symptoms (5.260.8 vs. 3.860.9 days; p50.20), or the number of prednisone bursts in past 6 months (0.7560.1 vs. 0.5360.10; p50.22) between allergen vs. viral-driven asthma respectively. In contrast, log mean FeNO levels increased from 23 to 57 vs. 20 to 25 ppb (p<0.0001) in allergen vs. viral-driven acute asthma respectively. CONCLUSIONS: FeNO is significantly elevated during allergen- but not viral-driven asthma exacerbations when compared to baseline. This suggests that eosinophilic inflammation plays are larger role in pathogenesis of allergen-driven vs. viral-mediated acute asthma in children.
504
Magnetic Resonance Imaging (MRI) Technique Detects Differences in Lung Function in Boys and Girls who are at Risk for Asthma E. L. Anderson1, M. D. Evans2, L. P. Salazar1, C. J. Tisler1, K. A. Roberg1, R. Gangnon2, D. J. Jackson1, J. E. Gern1, R. Lemanske, Jr, 1, S. B. Fain3; 1University of Wisconsin School of Medicine and Public Health, Madison, WI, 2University of Wisconsin Population Health
Sciences Biostatistics and Medical Informatics, Madison, WI, 3University of Wisconsin - Madison, Madison, WI. RATIONALE: Gender is one factor that has been associated with differential patterns of onset, severity, persistence, and remittance of asthma during childhood and beyond. Factors underlying these observations are incompletely understood. MRI has been utilized in adults with asthma as a non-invasive and sensitive technique to assess the anatomy of the airways as it relates to lung function. We hypothesized that children with asthma would demonstrate similar observed defect scores to those seen in adults with asthma. METHODS: 43 children ages 9-11 years were recruited from participants in the Childhood Origins of ASThma (COAST) project, an observational study of a high-risk birth cohort. MRI with NC100182-inhalation (hyperpolarized helium), an inert gas, was used to define the location and size of ventilation defects (areas of reduced or missing helium signal). Whole lung and lobar defect scores were determined by an individual blinded to the participants’ asthma phenotypes. RESULTS: Children with current asthma (n517) had significantly greater defect scores compared to children without asthma (n526) [11 vs. 6, (p50.01)]. Female gender was associated with significantly greater defect scores, regardless of asthma diagnosis [13 vs. 6, (p 5 0.02)]. Defect score tended to be correlated to FEV0.5 post-bronchodilator reversibility (r 5 0.33, p 5 0.06). CONCLUSION: Defects in lung ventilation were significantly more common in asthmatic children and in girls regardless of asthma status. These findings suggest that airway closure is not uniformly distributed throughout the lung in childhood asthma, and raises questions about regional differences in airway inflammation or anatomy that may be related to gender.
505
Most Nocturnal Asthma Symptoms Occur Outside of Exacerbations and Associate with Morbidity C. C. Horner1, D. Mauger2, R. C. Strunk1, N. J. Graber2, R. F. Lemanske, Jr, 3, C. A. Sorkness3, S. J. Szefler4, R. S. Zeiger5, L. M. Taussig6, L. B. Bacharier1; 1Washington University School of Medicine, Saint Louis, MO, 2Pennsylvania State University, Hershey, PA, 3University of Wisconsin, Madison, WI, 4National Jewish Health, Denver, CO, 5Univeristy of California, San Diego, CA, 6University of Denver, Denver, CO. RATIONALE: Although nocturnal awakenings help categorize asthma severity and control, their clinical significance has not been thoroughly studied. We sought to determine the clinical consequences of nocturnal asthma symptom(s) requiring albuterol in children with mild-to-moderate persistent asthma. METHODS: 285 children ages 6 to 14 years with mild-to-moderate persistent asthma were randomized to receive one of three controller regimens and completed daily symptom diaries for 48 weeks. Diary responses were analyzed for the frequency and consequences of nocturnal asthma symptoms requiring albuterol. RESULTS: Nocturnal asthma symptoms requiring albuterol occurred in 72.2% of participants at least once and in 24.3% of participants 13 times or more. 81% of nocturnal symptoms occurred outside of exacerbation periods and were associated the next day with the following events: albuterol use [56.9% of days preceded by nocturnal symptoms versus 18.1% of days not preceded by nocturnal symptoms; Relative Risk (RR)52.3; 95% CI:2.2, 2.4], school absence (5.0% versus 0.3%; RR510.6; 95% CI:7.8, 14.4), and doctor contact (3.7% versus 0.2%; RR58.8; 95% CI:6.1, 12.5). Relative risks for these morbidity factors were similar during exacerbation periods (RR51.7 for albuterol use, 5.5 for school absence, and 4.9 for doctor contact). Nocturnal symptoms did not predict the onset of an exacerbation. CONCLUSIONS: Nocturnal symptoms requiring albuterol in children with mild-to-moderate persistent asthma receiving controller therapy occurred predominantly outside of exacerbation periods. Despite being poor predictors of exacerbations, they were associated with increases in albuterol use, school absences, and doctor contacts the day after nocturnal symptom occurrences.
SUNDAY
Abstracts AB133
J ALLERGY CLIN IMMUNOL VOLUME 127, NUMBER 2
Cultured Human Mast Cells are heterogeneous for expression of the High Affinity IgE Receptor FceRI H. Hoffmann1, P. Munk Frandsen1, L. Harder Christensen2, R. Dahl1, P. Schiøtz1; 1Aarhus University, Aarhus, DENMARK, 2ALK-Abello, Hørsholm, DENMARK. RATIONALE: Mast cells expressing the high affinity IgE receptor (FceRI) are a cornerstone of the type I allergic reaction. We present data from cultured human mast cells suggesting that this is only one subtype of mast cells. We studied the response of mast cells through FceRI and effect of stabilization of surface expression of FceRI by IgE. METHODS: Mast cells were cultured from CD1331 progenitors from peripheral (PBMC) or cord blood. FceRI was stabilized with 2mg/ml IgE for 2 days. IgE density was measured with QiFiKit. Cells were activated by addition of anti-FceRI antibody in log dilutions from 1ng-10mg/ml, and labeled with anti-CD63 and anti-CD203c. Maximal activation, sensitivity and co-operativity were determined from non-linear curves fitted to activation data. RESULTS: All cultures were homogeneous for tryptase and metachromasy. Only cells expressing FceRI, but all cells expressing FceRI, were activated. PBMC bind 203 000 molecules IgE/cell. All cells binding IgE can be activated by crosslinking of FceRI to upregulate CD63. Expression of CD203c and histamine release correlates with expression of CD63. Stabilization of FceRI with IgE doubled the number of CD631 activatable cells (p50.0001), increased sensitivity and slope factor of PBMC six-fold. Anti-IgE reversed this effect (p50.0002), but did not reduce activation levels below that of cell lines not stabilized with IgE. CONCLUSIONS: The fraction of PBMC that binds high levels of IgE can be activated through FceRI. Baseline expression of FceRI is independent of anti-IgE. The fraction of PBMC that does not express FceRI has a different phenotype.
503
Is Exhaled Nitric Oxide (FeNO) Elevated in Children with Acute Asthma? J. Malka, J. R. Fish, P. Pickering, P. Ramamoorthy, M. Gleason, J. D. Spahn; National Jewish Health, Denver, CO. RATIONALE: There is conflicting data regarding whether exhaled nitric oxide (FeNO) levels are elevated in children presenting with acute asthma. METHODS: We sought to prospectively determine if FeNO levels are differentially elevated in children with viral- vs. allergen-driven acute asthma. 82 children with acute asthma completed a questionnaire regarding symptoms, albuterol use and whether the illness was associated with a viral-infection or allergen exposure, as well as spirometry & FeNO before and after prednisone (2 mg/kg/d) for 5 to 7 days. All children had baseline spirometry, FeNO and aeroallergen skin testing. RESULTS: The mean age was 11.6 1/- 3.3 years, 59% were male and 86% atopic. Baseline FeNO was 22 ppb increasing to 40 ppb during the exacerbation. There was no difference in the decline in FEV1 (19.363.3 vs. 25.363.0; p50.2) FEV1/FVC (10 6 2.1 vs. 10 6 2.4; p50.86), duration of nocturnal symptoms (5.260.8 vs. 3.860.9 days; p50.20), or the number of prednisone bursts in past 6 months (0.7560.1 vs. 0.5360.10; p50.22) between allergen vs. viral-driven asthma respectively. In contrast, log mean FeNO levels increased from 23 to 57 vs. 20 to 25 ppb (p<0.0001) in allergen vs. viral-driven acute asthma respectively. CONCLUSIONS: FeNO is significantly elevated during allergen- but not viral-driven asthma exacerbations when compared to baseline. This suggests that eosinophilic inflammation plays are larger role in pathogenesis of allergen-driven vs. viral-mediated acute asthma in children.
504
Magnetic Resonance Imaging (MRI) Technique Detects Differences in Lung Function in Boys and Girls who are at Risk for Asthma E. L. Anderson1, M. D. Evans2, L. P. Salazar1, C. J. Tisler1, K. A. Roberg1, R. Gangnon2, D. J. Jackson1, J. E. Gern1, R. Lemanske, Jr, 1, S. B. Fain3; 1University of Wisconsin School of Medicine and Public Health, Madison, WI, 2University of Wisconsin Population Health
Sciences Biostatistics and Medical Informatics, Madison, WI, 3University of Wisconsin - Madison, Madison, WI. RATIONALE: Gender is one factor that has been associated with differential patterns of onset, severity, persistence, and remittance of asthma during childhood and beyond. Factors underlying these observations are incompletely understood. MRI has been utilized in adults with asthma as a non-invasive and sensitive technique to assess the anatomy of the airways as it relates to lung function. We hypothesized that children with asthma would demonstrate similar observed defect scores to those seen in adults with asthma. METHODS: 43 children ages 9-11 years were recruited from participants in the Childhood Origins of ASThma (COAST) project, an observational study of a high-risk birth cohort. MRI with NC100182-inhalation (hyperpolarized helium), an inert gas, was used to define the location and size of ventilation defects (areas of reduced or missing helium signal). Whole lung and lobar defect scores were determined by an individual blinded to the participants’ asthma phenotypes. RESULTS: Children with current asthma (n517) had significantly greater defect scores compared to children without asthma (n526) [11 vs. 6, (p50.01)]. Female gender was associated with significantly greater defect scores, regardless of asthma diagnosis [13 vs. 6, (p 5 0.02)]. Defect score tended to be correlated to FEV0.5 post-bronchodilator reversibility (r 5 0.33, p 5 0.06). CONCLUSION: Defects in lung ventilation were significantly more common in asthmatic children and in girls regardless of asthma status. These findings suggest that airway closure is not uniformly distributed throughout the lung in childhood asthma, and raises questions about regional differences in airway inflammation or anatomy that may be related to gender.
505
Most Nocturnal Asthma Symptoms Occur Outside of Exacerbations and Associate with Morbidity C. C. Horner1, D. Mauger2, R. C. Strunk1, N. J. Graber2, R. F. Lemanske, Jr, 3, C. A. Sorkness3, S. J. Szefler4, R. S. Zeiger5, L. M. Taussig6, L. B. Bacharier1; 1Washington University School of Medicine, Saint Louis, MO, 2Pennsylvania State University, Hershey, PA, 3University of Wisconsin, Madison, WI, 4National Jewish Health, Denver, CO, 5Univeristy of California, San Diego, CA, 6University of Denver, Denver, CO. RATIONALE: Although nocturnal awakenings help categorize asthma severity and control, their clinical significance has not been thoroughly studied. We sought to determine the clinical consequences of nocturnal asthma symptom(s) requiring albuterol in children with mild-to-moderate persistent asthma. METHODS: 285 children ages 6 to 14 years with mild-to-moderate persistent asthma were randomized to receive one of three controller regimens and completed daily symptom diaries for 48 weeks. Diary responses were analyzed for the frequency and consequences of nocturnal asthma symptoms requiring albuterol. RESULTS: Nocturnal asthma symptoms requiring albuterol occurred in 72.2% of participants at least once and in 24.3% of participants 13 times or more. 81% of nocturnal symptoms occurred outside of exacerbation periods and were associated the next day with the following events: albuterol use [56.9% of days preceded by nocturnal symptoms versus 18.1% of days not preceded by nocturnal symptoms; Relative Risk (RR)52.3; 95% CI:2.2, 2.4], school absence (5.0% versus 0.3%; RR510.6; 95% CI:7.8, 14.4), and doctor contact (3.7% versus 0.2%; RR58.8; 95% CI:6.1, 12.5). Relative risks for these morbidity factors were similar during exacerbation periods (RR51.7 for albuterol use, 5.5 for school absence, and 4.9 for doctor contact). Nocturnal symptoms did not predict the onset of an exacerbation. CONCLUSIONS: Nocturnal symptoms requiring albuterol in children with mild-to-moderate persistent asthma receiving controller therapy occurred predominantly outside of exacerbation periods. Despite being poor predictors of exacerbations, they were associated with increases in albuterol use, school absences, and doctor contacts the day after nocturnal symptom occurrences.
SUNDAY
Abstracts AB133
J ALLERGY CLIN IMMUNOL VOLUME 127, NUMBER 2