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Food allergy [FA] is associated with potentially fatal childhood asthma [PFCA]
S144 Abstracts
Reduced Activation by Systemic Glucocorticoid of the AP-1 Component c-jun in Bronchial Mucosal Cells of GC Sensitive, but Not Resistant Asthmatics C. J. Corrigan, K. Mallett, T. Loke, J. Ratoff, B. O’Connor, T. Lee; Asthma, Allergy & Respiratory Science, Guy’s. King’s and St. Thomas’ School of Medicine, London, UNITED KINGDOM. RATIONALE: Our previous studies implicate the transcriptional regulatory factor AP-1, composed of c-fos and c-jun, in the regulation of the clinical response of asthmatics to systemic GC therapy. We hypothesised that c-fos expression and c-jun phosphorylation are increased in the bronchial mucosa of GC resistant, as compared with sensitive asthmatics and differentially regulated by systemic GC. METHODS: We used immunohistochemistry with validated antibodies and digital image analysis to measure the expression of c-fos and total and phosphorylated c-jun (c-junP) in mucosal inflammatory cells in endobronchial biopsies from 9 GC sensitive (∆FEV1>25%, age 35-67 yr) and 20 GC resistant (∆FEV1<15%, age 25-73 yr) asthmatics taken before and after 2 wk of therapy with oral prednisolone (1.72mg/m2 body surface area). Total leukocytes were enumerated using the pan-leukocyte marker CD45. RESULTS: Median total numbers of (CD45+) mucosal leukocytes were not altered by GC therapy in either group. At baseline, median total numbers of c-jun immunoreactive cells were elevated in the GC resistant, as compared with the sensitive asthmatics (p=0.015). In addition, median total numbers of c-junP immunoreactive cells (p=0.004), as well as the fraction of c-jun+ cells in which c-jun was phosphorylated (p=0.008) were significantly reduced, starting from a similar baseline, following prednisolone in the GC sensitive, but not the resistant asthmatics. The numbers of c-fos immunoreactive cells were similar in both groups at baseline, and did not significantly change following prednisolone. CONCLUSION: Clinical GC responsiveness in asthma is accompanied by reduced phosphorylation of bronchial mucosal c-jun, a phenomenon not seen in resistant patients. Funding: Asthma UK
573
Prevention of Pediatric Intensive Care Unit (PICU) Admissions: Focus on Improving Asthma Care Early in Exacerbations A. Elizur, L. B. Bacharier, R. C. Strunk; Pulmonary, Allergy and immunology, Children’s hospital, St Louis, MO. RATIONALE: Status asthmaticus is a frequent cause for admission to the PICU. Our goal was to characterize subgroups of patients admitted to the PICU with status asthmaticus and to identify risk factors for such admissions. METHODS: In a retrospective cohort study we reviewed charts of 56 consecutive patients 2-18 years old admitted to the PICU during a 1 year period (3/02-3/03) for status asthmaticus. Patients with chronic lung diseases other than asthma were excluded. RESULTS: 48 of 54 patients (89%) for whom baseline asthma severity could be determined had persistent asthma. Of these patients, 37.5% were not treated with daily inhaled Corticosteroids (ICS). Those not treated had history of fewer prior hospitalization (P<0.001), fewer prior PICU admissions (P=0.01) and less severe disease overall (P=0.012). However, the current exacerbation was comparable in both groups based upon length of symptoms prior to presentation (mean 2.6 vs. 2.7 days), vital signs on presentation (mean 02 saturation in R/A = 88% vs. 89%), length of stay in the PICU (mean 1.4 vs. 1.7 days), and treatment in the ED or PICU (e.g., 38.9% vs. 36.7% for IV Terbutaline and 16.7% vs. 20% for I/V MgSO4). Only 12/56 patients (1 of those without regular use of ICS and 11 with ICS) had received oral steroids prior to arrival to ED. CONCLUSIONS: Asthmatics with different disease severities can have similar severe exacerbations. Delays in treatment and under use of systemic steroids during acute exacerbations indicate that PICU admissions may be preventable in both types of patients.
574
J ALLERGY CLIN IMMUNOL FEBRUARY 2005
Impact of the Breathmobile on Baltimore City Children With Asthma M. E. Bollinger1, M. Foster2, D. Mebane2, K. Mudd1, J. Oakley1, M. Ramagopal1, C. Blaisdell1; 1University MD School of Medicine, Baltimore, MD, 2University MD Medical System, Baltimore, MD. RATIONALE: This study evaluated the impact of the University of Maryland Hospital for Children Breathmobile, a mobile clinic, that has provided asthma specialty services to children since 3/02. METHODS: Computerized medical records were analyzed between 3/01 and 1/04. Overall patient population was evaluated for baseline characteristics. A subset of children who received > 3 visits were analyzed at baseline and after 3 visits for asthma severity, medication use, urgent care visits, and missed school days. RESULTS: From 3/01-1/04, 440 children were evaluated with a mean age of 8 yrs (range 3-18), 46.4% female, 91.6% African American, >60% Medicaid and 70% with persistent asthma. At baseline, 20.9% were on albuterol alone and 9.8% on no medications. Baseline data (mean, range) included annual lost school days (7.4, 0-100), lifetime ED visits (6.9, 0-100), hospitalizations (1.6, 0-35) and oral steroid courses (4.4, 0-60). Skin testing revealed 83.6% with at least one positive test (54.3% + cockroach and > 40% + to mouse, tree and dust mite). For the 114 children seen for > 3 visits the # of school days missed decreased to an average of 2.6/year. Mean annual ED visits for this group were 0.58 (range 0-8), hospitalizations 0.07 (range 0-3) and oral steroids 0.72 (0-11). Asthma severity decreased from > 50% moderate/severe at baseline to 71.8% mild after >3 visits with 89% on controller medications. CONCLUSIONS: During the first 2 years of the program, the Baltimore Breathmobile has seen increased use of controller medications, decreased missed school days and decreased asthma morbidity. Funding: Maryland Tobacco Restitution Fund
575
MONDAY
Food Allergy [FA] Is Associated With Potentially Fatal Childhood Asthma [PFCA] H. T. Katz1, N. M. Vogel2, D. M. Lang2; 1Pulmonology, Allergy & Immunology, Nemours Children’s Clinic, Jacksonville, FL, 2Pulmonary, Allergy & Critical Care Medicine, Cleveland Clinic Foundation, Cleveland, OH. RATIONALE: Risk factors for PFCA are incompletely understood. FA has previously been associated with PFCA in a report from London (JACI 2003;112:168). We assessed associations with PFCA in an urban US population. METHODS: Medical records from 72 patients admitted to our pediatric intensive care unit (PICU) for asthmatic exacerbation over a 10-year period were reviewed. These were compared in a case-control design with 2 randomly selected groups of 108 patients (1.5x): 1) patients admitted to regular nursing floor (RNF) for asthma and never requiring PICU admission; 2) ambulatory patients (AMB) without prior asthma hospitalization. Data were analyzed by logistic regression in a model with age, gender, race, season of admission, FA, psychologic comorbidity, smoking, and inhaled steroid exposure (ISE). RESULTS: FA was more frequent in PICU than RNF or AMB patients (p<.01); egg, peanut, seafood, milk, and tree nut accounted for 85% of FA. Compared with RNF, PICU admission was associated with FA (p=.003) and older age (p=.009); compared with AMB, PICU admission was associated with FA (p<.001), African-American race (p<.001), and younger age (p=.01). Among those hospitalized in PICU or RNF, FA tended only to be associated with ISE (p=.077). Compared with AMB, RNF admission was associated with African-American race (p<.001) and younger age (p<.001), but not FA (p=.29). CONCLUSIONS: Our findings provide further support for FA as a risk factor for PFCA, and suggest that asthmatic children or adolescents with FA are a target population for more aggressive asthma management.
576
Reduced Activation by Systemic Glucocorticoid of the AP-1 Component c-jun in Bronchial Mucosal Cells of GC Sensitive, but Not Resistant Asthmatics C. J. Corrigan, K. Mallett, T. Loke, J. Ratoff, B. O’Connor, T. Lee; Asthma, Allergy & Respiratory Science, Guy’s. King’s and St. Thomas’ School of Medicine, London, UNITED KINGDOM. RATIONALE: Our previous studies implicate the transcriptional regulatory factor AP-1, composed of c-fos and c-jun, in the regulation of the clinical response of asthmatics to systemic GC therapy. We hypothesised that c-fos expression and c-jun phosphorylation are increased in the bronchial mucosa of GC resistant, as compared with sensitive asthmatics and differentially regulated by systemic GC. METHODS: We used immunohistochemistry with validated antibodies and digital image analysis to measure the expression of c-fos and total and phosphorylated c-jun (c-junP) in mucosal inflammatory cells in endobronchial biopsies from 9 GC sensitive (∆FEV1>25%, age 35-67 yr) and 20 GC resistant (∆FEV1<15%, age 25-73 yr) asthmatics taken before and after 2 wk of therapy with oral prednisolone (1.72mg/m2 body surface area). Total leukocytes were enumerated using the pan-leukocyte marker CD45. RESULTS: Median total numbers of (CD45+) mucosal leukocytes were not altered by GC therapy in either group. At baseline, median total numbers of c-jun immunoreactive cells were elevated in the GC resistant, as compared with the sensitive asthmatics (p=0.015). In addition, median total numbers of c-junP immunoreactive cells (p=0.004), as well as the fraction of c-jun+ cells in which c-jun was phosphorylated (p=0.008) were significantly reduced, starting from a similar baseline, following prednisolone in the GC sensitive, but not the resistant asthmatics. The numbers of c-fos immunoreactive cells were similar in both groups at baseline, and did not significantly change following prednisolone. CONCLUSION: Clinical GC responsiveness in asthma is accompanied by reduced phosphorylation of bronchial mucosal c-jun, a phenomenon not seen in resistant patients. Funding: Asthma UK
573
Prevention of Pediatric Intensive Care Unit (PICU) Admissions: Focus on Improving Asthma Care Early in Exacerbations A. Elizur, L. B. Bacharier, R. C. Strunk; Pulmonary, Allergy and immunology, Children’s hospital, St Louis, MO. RATIONALE: Status asthmaticus is a frequent cause for admission to the PICU. Our goal was to characterize subgroups of patients admitted to the PICU with status asthmaticus and to identify risk factors for such admissions. METHODS: In a retrospective cohort study we reviewed charts of 56 consecutive patients 2-18 years old admitted to the PICU during a 1 year period (3/02-3/03) for status asthmaticus. Patients with chronic lung diseases other than asthma were excluded. RESULTS: 48 of 54 patients (89%) for whom baseline asthma severity could be determined had persistent asthma. Of these patients, 37.5% were not treated with daily inhaled Corticosteroids (ICS). Those not treated had history of fewer prior hospitalization (P<0.001), fewer prior PICU admissions (P=0.01) and less severe disease overall (P=0.012). However, the current exacerbation was comparable in both groups based upon length of symptoms prior to presentation (mean 2.6 vs. 2.7 days), vital signs on presentation (mean 02 saturation in R/A = 88% vs. 89%), length of stay in the PICU (mean 1.4 vs. 1.7 days), and treatment in the ED or PICU (e.g., 38.9% vs. 36.7% for IV Terbutaline and 16.7% vs. 20% for I/V MgSO4). Only 12/56 patients (1 of those without regular use of ICS and 11 with ICS) had received oral steroids prior to arrival to ED. CONCLUSIONS: Asthmatics with different disease severities can have similar severe exacerbations. Delays in treatment and under use of systemic steroids during acute exacerbations indicate that PICU admissions may be preventable in both types of patients.
574
J ALLERGY CLIN IMMUNOL FEBRUARY 2005
Impact of the Breathmobile on Baltimore City Children With Asthma M. E. Bollinger1, M. Foster2, D. Mebane2, K. Mudd1, J. Oakley1, M. Ramagopal1, C. Blaisdell1; 1University MD School of Medicine, Baltimore, MD, 2University MD Medical System, Baltimore, MD. RATIONALE: This study evaluated the impact of the University of Maryland Hospital for Children Breathmobile, a mobile clinic, that has provided asthma specialty services to children since 3/02. METHODS: Computerized medical records were analyzed between 3/01 and 1/04. Overall patient population was evaluated for baseline characteristics. A subset of children who received > 3 visits were analyzed at baseline and after 3 visits for asthma severity, medication use, urgent care visits, and missed school days. RESULTS: From 3/01-1/04, 440 children were evaluated with a mean age of 8 yrs (range 3-18), 46.4% female, 91.6% African American, >60% Medicaid and 70% with persistent asthma. At baseline, 20.9% were on albuterol alone and 9.8% on no medications. Baseline data (mean, range) included annual lost school days (7.4, 0-100), lifetime ED visits (6.9, 0-100), hospitalizations (1.6, 0-35) and oral steroid courses (4.4, 0-60). Skin testing revealed 83.6% with at least one positive test (54.3% + cockroach and > 40% + to mouse, tree and dust mite). For the 114 children seen for > 3 visits the # of school days missed decreased to an average of 2.6/year. Mean annual ED visits for this group were 0.58 (range 0-8), hospitalizations 0.07 (range 0-3) and oral steroids 0.72 (0-11). Asthma severity decreased from > 50% moderate/severe at baseline to 71.8% mild after >3 visits with 89% on controller medications. CONCLUSIONS: During the first 2 years of the program, the Baltimore Breathmobile has seen increased use of controller medications, decreased missed school days and decreased asthma morbidity. Funding: Maryland Tobacco Restitution Fund
575
MONDAY
Food Allergy [FA] Is Associated With Potentially Fatal Childhood Asthma [PFCA] H. T. Katz1, N. M. Vogel2, D. M. Lang2; 1Pulmonology, Allergy & Immunology, Nemours Children’s Clinic, Jacksonville, FL, 2Pulmonary, Allergy & Critical Care Medicine, Cleveland Clinic Foundation, Cleveland, OH. RATIONALE: Risk factors for PFCA are incompletely understood. FA has previously been associated with PFCA in a report from London (JACI 2003;112:168). We assessed associations with PFCA in an urban US population. METHODS: Medical records from 72 patients admitted to our pediatric intensive care unit (PICU) for asthmatic exacerbation over a 10-year period were reviewed. These were compared in a case-control design with 2 randomly selected groups of 108 patients (1.5x): 1) patients admitted to regular nursing floor (RNF) for asthma and never requiring PICU admission; 2) ambulatory patients (AMB) without prior asthma hospitalization. Data were analyzed by logistic regression in a model with age, gender, race, season of admission, FA, psychologic comorbidity, smoking, and inhaled steroid exposure (ISE). RESULTS: FA was more frequent in PICU than RNF or AMB patients (p<.01); egg, peanut, seafood, milk, and tree nut accounted for 85% of FA. Compared with RNF, PICU admission was associated with FA (p=.003) and older age (p=.009); compared with AMB, PICU admission was associated with FA (p<.001), African-American race (p<.001), and younger age (p=.01). Among those hospitalized in PICU or RNF, FA tended only to be associated with ISE (p=.077). Compared with AMB, RNF admission was associated with African-American race (p<.001) and younger age (p<.001), but not FA (p=.29). CONCLUSIONS: Our findings provide further support for FA as a risk factor for PFCA, and suggest that asthmatic children or adolescents with FA are a target population for more aggressive asthma management.
576