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The “Epidemic” of Eosinophilic Esophagitis (EE) is due to Increased Recognition of a Chronic Disorder
Abstracts AB233
J ALLERGY CLIN IMMUNOL VOLUME 125, NUMBER 2
910
Ozone Exposure Enhances Airway Eosinophilia in Atopic Asthmatic Individuals M. Hernandez1,2, N. Alexis1,2, J. C. Lay1,2, B. Harris1,2, D. Peden1,2; 1 University of North Carolina at Chapel Hill, Chapel Hill, NC, 2Center for Environmental Medicine, Asthma, & Lung Biology, Chapel Hill, NC. RATIONALE: Human challenge studies of both asthmatic and non-asthmatic adults have revealed three distinct responses following ozone challenge: an immediate decrease in lung function; increased bronchial reactivity; and increases in airway inflammation typified by increased influx of neutrophils. There are variable reports that ozone modifies eosinophilic inflammation in the lower airways of atopic volunteers. We hypothesized that underlying allergic airways inflammation would modify response to ozone exposure. METHODS: 24 normal volunteers, 13 volunteers with + skin tests, and 11 volunteers with + skin tests and mild asthma were exposed to 0.4 ppm ozone for 2 hours. Sputum induction was done the day prior to ozone exposure and 6 hours after ozone exposure. Cell counts and differentials as well as cytokine assessments were obtained on sputum samples from all subjects. Within group comparisons were made between pre exposure and post ozone values for a given endpoint with paired T tests. Across groups, comparisons of the change from baseline due to ozone for a given endpoint were made to determine if atopy or asthma status modifies response to ozone. RESULTS: Subjects in each group had a statistically significant increase in induced sputum neutrophils (p<0.01) and decreased macrophages (p<0.01) 6 hours after ozone exposure. Atopic asthmatic subjects had a statistically significant increase in sputum eosinophils (p50.04) compared to normal volunteers. Atopic subjects experienced a statistically significant increase in induced sputum IL-5 (p50.05). CONCLUSIONS: Based on increases in sputum eosinophils and sputum IL-5, ozone has the potential to aggravate underlying allergic airways inflammation in atopic individuals.
912
911
913
The ``Epidemic'' of Eosinophilic Esophagitis (EE) is due to Increased Recognition of a Chronic Disorder C. W. DeBrosse, M. H. Collins, B. Buckmeier, A. Greenburg, C. Allen, J. Abonia, A. Assa’ad, J. P. Franciosi, M. E. Rothenberg; Cincinnati Children’s Hospital Medical Center, Cincinnati, OH. RATIONALE: Eosinophilic Esophagitis (EE) is a recently recognized disorder that is now commonly occurring. The reason for the sudden burst of cases has not been determined. METHODS: Esophageal biopsies obtained between 1982-1999 with chronic inflammation were re-examined and re-classified as retrospective EE (rEE) if 15 eosinophils/hpf or chronic esophagitis (CE) if < 15 eosinophils/hpf. Descriptive and analytic statistical methods were utilized for both the entire cohort and a population based cohort. RESULTS: Of 3,818 biopsies obtained, 880 from 666 patients were re-examined; 198 patients were re-classified as having rEE. From 1982-1999, in a population-based cohort, the incidence rate was 0/100,000 children in 1982 vs 4.9/100,000 children in 1996 (peak); (p < 0.001; IRR 1.18; CI 1.09-1.28). After correcting for a 40-fold increase in the number of endoscopies during this time period, the proportion of rEE did not change (0.08 in 1982 vs 0.08 in 1996 (peak); p 5 0.9; IRR 1.02; CI 0.73 -1.44). Interestingly, patients with > 5 eos/hpf were more likely to have persistent esophageal eosinophilia on repeat EGD (p < 0.0001; OR 7.78; CI 3.69 -25.86) and were more likely have evidence of basal cell hyperplasia (76% vs 6%; p <0.001; OR 51.40; CI 30.66 - 86.10) or lamina propria fibrosis (28% vs 5%; p <0.001; OR 12.80; CI 6.12 - 26.75). CONCLUSIONS: The perceived epidemic of EE is due to increased recognition of a chronic disorder. Patients with > 5 eos/hpf are at increased risk of persistent esophageal eosinophilia and have histologic features associated with EE.
TUESDAY
Particulate Matter Induced Airway Epithelial Barrier Dysfunction F. Rezaee1, L. B. Lerner1, A. L. Ivanov1, P. Breysse2, L. A. Beck1, S. N. Georas1; 1University of Rochester Medical Center, Rochester, NY, 2Johns Hopkins University, Baltimore, MD. RATIONALE: Disruption of epithelial barrier function is emerging as an important risk factor for allergen sensitization and asthma, probably by promoting the uptake of inhaled allergens by subepithelial dendritic cells. Ambient particulate matter (PM) is now strongly associated with both asthma incidence and exacerbations, and is thought to function as an inhaled pro-Th2 adjuvant. Whether PM induces airway epithelial barrier dysfunction is currently unknown. METHODS: 16HBE human bronchial epithelial cells were grown to confluence on TranswellÒ inserts, and transepithelial electrical resistance (TEER) measured as a marker of barrier function. Expression of tight junction proteins including zona occludens-1 (ZO-1), claudin-1, occludin, and E-cadherin was analyzed by Western blot. Cells were exposed to an aqueous solution of ambient outdoor PM collected from Baltimore, MD for different time points at concentrations thought to reflect those found in human airways (3, 10, 30 mcg/cm2). In some experiments, cells were preincubated in low calcium medium prior to addition of PM to investigate tight junction downregulation and recovery. RESULTS: PM exposure caused a reduction in TEER of about 20-30% between 1 and 24 hours. This was associated with reduced ZO-1 expression as determined by Western blot. Calcium depletion reproducibly disrupted barrier function, and co-incubation with PM during calcium repletion dose-dependently inhibited barrier recovery for up to 30 hours. CONCLUSIONS: Ambient PM induces bronchial epithelial barrier dysfunction in vitro using models of both barrier disruption as well as barrier recovery. These previously unreported properties of PM may contribute to the pro-allergic adjuvant effects of PM in urban areas.
The Impact of School Proximity to Freeways on Asthma Prevalence and Asthma Control C. Kuo1, R. Huynh1, C. Luu1, T. Morphew2, L. Scott2, P. Huynh2; 1 Harbor-UCLA Medical Center, Torrance, CA, 2University of Southern California, Los Angeles, CA. RATIONALE: A growing body of evidence demonstrates adverse respiratory health effects in children living in proximity to residential heavy traffic exposure. School age children spend the majority of their daytime hours at school. To the best of our knowledge, no large-scale studies have evaluated the association between school distance to nearby freeways and asthma prevalence and control. METHOD: A bilingual, seven-question, self-administered asthma screening survey validated for the identification and assessment of asthma was used to identify children with asthma and with likelihood of poor disease control (sensitivity 86.5%, specificity 83.6%). Results were correlated with the shortest linear distance between a child’s school and the nearest major freeway. RESULTS: 10,874 surveys were analyzed from 739 classrooms in 20 inner-city elementary schools. Results identified 2530 (23.3%) elementary school children likely to have asthma, of whom 1316 (52%) were likely to have controlled asthma. Of 1214 (48%) children likely to have uncontrolled asthma, 768 (63%) were likely to have moderate-to-severe disease activity. Children attending schools within 2 miles of a freeway had increased likelihood of asthma detection (p<0.0001) compared to children who attended schools greater than 2 miles from the nearest freeway. Similarly, for children likely to have asthma, attending schools within 2 miles of a freeway was associated with an increased incidence of uncontrolled asthma (p50.005) and moderate-to-severe disease (p50.005). CONCLUSIONS: Our study detected a 23.3% prevalence rate of asthma for inner-city Los Angeles elementary school children. Our results illustrate a statistically significant inverse relationship between school proximity to freeway and asthma prevalence and control.
J ALLERGY CLIN IMMUNOL VOLUME 125, NUMBER 2
910
Ozone Exposure Enhances Airway Eosinophilia in Atopic Asthmatic Individuals M. Hernandez1,2, N. Alexis1,2, J. C. Lay1,2, B. Harris1,2, D. Peden1,2; 1 University of North Carolina at Chapel Hill, Chapel Hill, NC, 2Center for Environmental Medicine, Asthma, & Lung Biology, Chapel Hill, NC. RATIONALE: Human challenge studies of both asthmatic and non-asthmatic adults have revealed three distinct responses following ozone challenge: an immediate decrease in lung function; increased bronchial reactivity; and increases in airway inflammation typified by increased influx of neutrophils. There are variable reports that ozone modifies eosinophilic inflammation in the lower airways of atopic volunteers. We hypothesized that underlying allergic airways inflammation would modify response to ozone exposure. METHODS: 24 normal volunteers, 13 volunteers with + skin tests, and 11 volunteers with + skin tests and mild asthma were exposed to 0.4 ppm ozone for 2 hours. Sputum induction was done the day prior to ozone exposure and 6 hours after ozone exposure. Cell counts and differentials as well as cytokine assessments were obtained on sputum samples from all subjects. Within group comparisons were made between pre exposure and post ozone values for a given endpoint with paired T tests. Across groups, comparisons of the change from baseline due to ozone for a given endpoint were made to determine if atopy or asthma status modifies response to ozone. RESULTS: Subjects in each group had a statistically significant increase in induced sputum neutrophils (p<0.01) and decreased macrophages (p<0.01) 6 hours after ozone exposure. Atopic asthmatic subjects had a statistically significant increase in sputum eosinophils (p50.04) compared to normal volunteers. Atopic subjects experienced a statistically significant increase in induced sputum IL-5 (p50.05). CONCLUSIONS: Based on increases in sputum eosinophils and sputum IL-5, ozone has the potential to aggravate underlying allergic airways inflammation in atopic individuals.
912
911
913
The ``Epidemic'' of Eosinophilic Esophagitis (EE) is due to Increased Recognition of a Chronic Disorder C. W. DeBrosse, M. H. Collins, B. Buckmeier, A. Greenburg, C. Allen, J. Abonia, A. Assa’ad, J. P. Franciosi, M. E. Rothenberg; Cincinnati Children’s Hospital Medical Center, Cincinnati, OH. RATIONALE: Eosinophilic Esophagitis (EE) is a recently recognized disorder that is now commonly occurring. The reason for the sudden burst of cases has not been determined. METHODS: Esophageal biopsies obtained between 1982-1999 with chronic inflammation were re-examined and re-classified as retrospective EE (rEE) if 15 eosinophils/hpf or chronic esophagitis (CE) if < 15 eosinophils/hpf. Descriptive and analytic statistical methods were utilized for both the entire cohort and a population based cohort. RESULTS: Of 3,818 biopsies obtained, 880 from 666 patients were re-examined; 198 patients were re-classified as having rEE. From 1982-1999, in a population-based cohort, the incidence rate was 0/100,000 children in 1982 vs 4.9/100,000 children in 1996 (peak); (p < 0.001; IRR 1.18; CI 1.09-1.28). After correcting for a 40-fold increase in the number of endoscopies during this time period, the proportion of rEE did not change (0.08 in 1982 vs 0.08 in 1996 (peak); p 5 0.9; IRR 1.02; CI 0.73 -1.44). Interestingly, patients with > 5 eos/hpf were more likely to have persistent esophageal eosinophilia on repeat EGD (p < 0.0001; OR 7.78; CI 3.69 -25.86) and were more likely have evidence of basal cell hyperplasia (76% vs 6%; p <0.001; OR 51.40; CI 30.66 - 86.10) or lamina propria fibrosis (28% vs 5%; p <0.001; OR 12.80; CI 6.12 - 26.75). CONCLUSIONS: The perceived epidemic of EE is due to increased recognition of a chronic disorder. Patients with > 5 eos/hpf are at increased risk of persistent esophageal eosinophilia and have histologic features associated with EE.
TUESDAY
Particulate Matter Induced Airway Epithelial Barrier Dysfunction F. Rezaee1, L. B. Lerner1, A. L. Ivanov1, P. Breysse2, L. A. Beck1, S. N. Georas1; 1University of Rochester Medical Center, Rochester, NY, 2Johns Hopkins University, Baltimore, MD. RATIONALE: Disruption of epithelial barrier function is emerging as an important risk factor for allergen sensitization and asthma, probably by promoting the uptake of inhaled allergens by subepithelial dendritic cells. Ambient particulate matter (PM) is now strongly associated with both asthma incidence and exacerbations, and is thought to function as an inhaled pro-Th2 adjuvant. Whether PM induces airway epithelial barrier dysfunction is currently unknown. METHODS: 16HBE human bronchial epithelial cells were grown to confluence on TranswellÒ inserts, and transepithelial electrical resistance (TEER) measured as a marker of barrier function. Expression of tight junction proteins including zona occludens-1 (ZO-1), claudin-1, occludin, and E-cadherin was analyzed by Western blot. Cells were exposed to an aqueous solution of ambient outdoor PM collected from Baltimore, MD for different time points at concentrations thought to reflect those found in human airways (3, 10, 30 mcg/cm2). In some experiments, cells were preincubated in low calcium medium prior to addition of PM to investigate tight junction downregulation and recovery. RESULTS: PM exposure caused a reduction in TEER of about 20-30% between 1 and 24 hours. This was associated with reduced ZO-1 expression as determined by Western blot. Calcium depletion reproducibly disrupted barrier function, and co-incubation with PM during calcium repletion dose-dependently inhibited barrier recovery for up to 30 hours. CONCLUSIONS: Ambient PM induces bronchial epithelial barrier dysfunction in vitro using models of both barrier disruption as well as barrier recovery. These previously unreported properties of PM may contribute to the pro-allergic adjuvant effects of PM in urban areas.
The Impact of School Proximity to Freeways on Asthma Prevalence and Asthma Control C. Kuo1, R. Huynh1, C. Luu1, T. Morphew2, L. Scott2, P. Huynh2; 1 Harbor-UCLA Medical Center, Torrance, CA, 2University of Southern California, Los Angeles, CA. RATIONALE: A growing body of evidence demonstrates adverse respiratory health effects in children living in proximity to residential heavy traffic exposure. School age children spend the majority of their daytime hours at school. To the best of our knowledge, no large-scale studies have evaluated the association between school distance to nearby freeways and asthma prevalence and control. METHOD: A bilingual, seven-question, self-administered asthma screening survey validated for the identification and assessment of asthma was used to identify children with asthma and with likelihood of poor disease control (sensitivity 86.5%, specificity 83.6%). Results were correlated with the shortest linear distance between a child’s school and the nearest major freeway. RESULTS: 10,874 surveys were analyzed from 739 classrooms in 20 inner-city elementary schools. Results identified 2530 (23.3%) elementary school children likely to have asthma, of whom 1316 (52%) were likely to have controlled asthma. Of 1214 (48%) children likely to have uncontrolled asthma, 768 (63%) were likely to have moderate-to-severe disease activity. Children attending schools within 2 miles of a freeway had increased likelihood of asthma detection (p<0.0001) compared to children who attended schools greater than 2 miles from the nearest freeway. Similarly, for children likely to have asthma, attending schools within 2 miles of a freeway was associated with an increased incidence of uncontrolled asthma (p50.005) and moderate-to-severe disease (p50.005). CONCLUSIONS: Our study detected a 23.3% prevalence rate of asthma for inner-city Los Angeles elementary school children. Our results illustrate a statistically significant inverse relationship between school proximity to freeway and asthma prevalence and control.