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Delayed Anaphylactic Reactions to Mammalian Meat are not Associated with an Increased Prevalence of Asthma
AB4 Abstracts
SATURDAY
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Delayed Anaphylactic Reactions to Mammalian Meat are not Associated with an Increased Prevalence of Asthma L. A. Kelly, S. L. Pochan, H. R. James, L. J. Workman, P. W. Heymann, S. P. Commins, T. A. E. Platts-Mills; University of Virginia, Charlottesville, VA. RATIONALE: In contrast to most food allergic patients, relatively few patients with delayed anaphylaxis after ingestion of mammalian meat and IgE specific for galactose-alpha-1,3-galactose (a-gal) suffer from atopic diseases. While these individuals frequently have IgE to cat, only a minority report symptoms of asthma. METHODS: Sera from 97 subjects with mammalian meat allergy, 42 asthmatics, and 52 controls were assayed for total serum IgE and IgE to a-gal and several inhalant allergens. Spirometry and eNO were performed as markers of asthma. RESULTS: The prevalence of asthma amongst these meat allergic subjects was 17%, surprisingly low given that 86% of these subjects have IgE to cat epithelium. The mean FEV1/FVC amongst meat allergic subjects was 0.78, not significantly different from controls at 0.82 (p5NS), compared to 0.72 in asthmatics (p50.02). Likewise, the mean eNO of meat allergic subjects was 22 ppb (16 ppb in controls, p5NS), significantly lower than that of asthmatics at 56 ppb (p50.001). While most had IgE to cat epithelium, only 22% had IgE to Fel d 1, the difference attributed to a-gal moieties present in cat epithelium. Separating out those subjects with IgE to both a-gal and cat epithelium, but not Fel d 1, who were living with a cat in the home, we found the prevalence of asthma dropped to 9%, mean FEV1 of 101%, FEV1/FVC 0.81, and eNO 18 ppb. CONCLUSIONS: Despite a history of food-related urticaria, angioedema, and anaphylaxis, elevated total IgE, and IgE to cat, patients with mammalian food allergy do not have increased risk for asthma.
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Intra-Individual Variation in DNA Methylation of IFNg and IL4 Over Days J. S. Kuriakose, D. Torrone, K. Gauvey-Kern, S. Hsu, M. Niedzwiecki, H. Jiang, F. Perera, R. L. Miller; Columbia University College of Physicians & Surgeons, New York, NY. RATIONALE: The mechanisms linking environmental exposure with asthma are complex and may involve epigenetic regulation of inflammatory genes. Using buccal cells as a sentinel population representative of changes in airways, we hypothesized epigenetic marks in allergic inflammatory genes in buccal DNA can vary over several days. METHODS: Buccal DNA was collected twice, 4-7 days apart from 8 nonsmoking adults and 4 children, from the Columbia Center for Children’s Environmental Health cohort. Methylation analysis using bisulfite conversion followed by pyrosequencing was performed on select CpG sites within the proximal promoter of the IFNg gene and the proximal promoter and second intron of the IL4 gene. RESULTS: Percent cytosine methylation (%5 mC) of IFNg ranged from 5979% for CpG-186 and 72-91% for CpG-295. Within the IL4 proximal promoter, %5 mC ranged from 56-100% for CpG-144, CpG-113, CpG-60, and CpG-12. Within the IL4 second intron, %5 mC ranged from 66-100% for CpG+1018, CpG+1064, CpG +969, CpG+1082, CpG-113, CpG+997, CpG+959, CpG+1044 and CpG+1001. After 4-7 days: %5 mC of IL4 at CpG-60 was decreased (mean difference (MD)5 4.9%5 mC, P50.045; Wilcoxon Rank Sum); %5 mC of IL4 at CpG+1082 was decreased (MD 5 3.1 %5 mC; P50.038). The %5 mC of IFNg at CpG-186 and CpG-295 increased (MD55%5 mC and 9.6%5 mC; P50.06 and 0.18, respectively). CONCLUSIONS: Individual buccal DNA methylation changes were found in CpG sites in the proximal promoter of IFNg, IL4, and second intron of IL4 after several days. Pilot data suggest DNA methylation may be dynamic and influenced by recent environmental exposures.
J ALLERGY CLIN IMMUNOL FEBRUARY 2011
Exploring The Novel Il-17-producing Cd4+TH2 Memory Cell Subset In Clinically Defined Asthmatic Patients. B. Uygungil1, J. A. Bernstein2, Y. Wang1; 1Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, 2University of Cincinnati, Cincinnati, OH. RATIONALE: In prior studies, we identified a subset of circulating human CD4+T cells expressing CRTH2, the prostaglandin D2 receptor, and CCR6 that are IL-17-TH2 memory cells featuring concurrent TH17 and TH2 cytokine production. In a mouse model of allergic lung disease, we showed that antigen specific IL-17-producing TH2 memory cells induced profound influx of heterogeneous inflammatory leukocytes and exacerbated pathology, suggesting a potential role of IL-17-TH2 memory cells in promoting the chronic asthma. Based on these mouse and human studies, we hypothesize that the occurrence of IL-17-TH2 memory cells in blood will be associated with the symptoms of clinically well-defined asthmatic patients. METHODS: A cross-sectional study is being conducted on adult asthma _ 12% patients 18-65 years of age with evidence of airway obstruction and > change in FEV1 post-bronchodilators. Atopy is defined as positive skin prick tests to two or more aeroallergens. The frequency of IL-17-TH2 memory cells in peripheral blood is examined using multicolor immunofluorescence analysis. RESULTS: The average age of atopic asthma patients analyzed thus far was 49 years and 75% were female. The frequency of IL-17-TH2 memory cells within the total CD4+TH2 memory pool were higher in atopic asthma patients (33% 69.7; n532) compared to a group of non-allergic, non-asthmatic donors (16% 67.6; n516). CONCLUSIONS: These preliminary results reveal that atopic asthma patients have greater IL-17-TH2 memory cells than normal controls. Larger numbers of non-atopic asthma and atopic non-asthma patient groups will be included in this ongoing analysis to elucidate whether this marker helps define asthma control on a cellular level.
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Persistent High FeNO Phenotype in Asthma I. O. Agache, C. Ciobanu; Transylvania University Brasov, Faculty of Medicine, Brasov, ROMANIA. RATIONALE: Exhaled NO (FeNO) was validated as a marker for eosinophilc inflammation and for predicting response to inhaled corticosteroids (ICS), but FeNO use for tailoring treatment gave conflicting results. The implications of the persistent high FeNO phenotype in asthma have not been yet evaluated. METHODS: FeNO was measured serially for at least 4 times at 3-4 months interval in 91children (5-16 years old) and 165 adult asthmatics treated with an ICS 6LABA/LTRA at a dosage recommended by GINA guidelines to achieve asthma control. Subjects with persistent high FeNO (above 45 ppb at all the serial measurements done) were compared with asthmatics with low FeNO (<25 ppb) for male sex, obesity, atopy, allergen exposure, moderate/severe persistent rhinitis, mean ACT score, severe asthma exacerbations, persistent low FEV1 (100 ml/year). Statistics by Chi test. RESULTS:9(9.89%) children and 31(18.79%) adults had persistent high FeNO. In children obesity (p50.0062) and in adults atopy (p50.0066) and low ACT score (p50.0000) were significantly higher in subjects with persistent high FeNO phenotype. Both in children and in adults the incidences of persistent low FEV1 (children p50.0109, adults p50.0438) and of the fast FEV1 decline (children p50.0000, adults p50.0011) were significant. There was no impact on the incidence of severe asthma exacerbations. CONCLUSIONS: Persistent high FeNO has distinct phenotypic traits in asthmatic children compared with adults. Both in children and in adults persistent high FeNO is associated with poor lung function and in adults with low ACT score.
SATURDAY
1
Delayed Anaphylactic Reactions to Mammalian Meat are not Associated with an Increased Prevalence of Asthma L. A. Kelly, S. L. Pochan, H. R. James, L. J. Workman, P. W. Heymann, S. P. Commins, T. A. E. Platts-Mills; University of Virginia, Charlottesville, VA. RATIONALE: In contrast to most food allergic patients, relatively few patients with delayed anaphylaxis after ingestion of mammalian meat and IgE specific for galactose-alpha-1,3-galactose (a-gal) suffer from atopic diseases. While these individuals frequently have IgE to cat, only a minority report symptoms of asthma. METHODS: Sera from 97 subjects with mammalian meat allergy, 42 asthmatics, and 52 controls were assayed for total serum IgE and IgE to a-gal and several inhalant allergens. Spirometry and eNO were performed as markers of asthma. RESULTS: The prevalence of asthma amongst these meat allergic subjects was 17%, surprisingly low given that 86% of these subjects have IgE to cat epithelium. The mean FEV1/FVC amongst meat allergic subjects was 0.78, not significantly different from controls at 0.82 (p5NS), compared to 0.72 in asthmatics (p50.02). Likewise, the mean eNO of meat allergic subjects was 22 ppb (16 ppb in controls, p5NS), significantly lower than that of asthmatics at 56 ppb (p50.001). While most had IgE to cat epithelium, only 22% had IgE to Fel d 1, the difference attributed to a-gal moieties present in cat epithelium. Separating out those subjects with IgE to both a-gal and cat epithelium, but not Fel d 1, who were living with a cat in the home, we found the prevalence of asthma dropped to 9%, mean FEV1 of 101%, FEV1/FVC 0.81, and eNO 18 ppb. CONCLUSIONS: Despite a history of food-related urticaria, angioedema, and anaphylaxis, elevated total IgE, and IgE to cat, patients with mammalian food allergy do not have increased risk for asthma.
2
Intra-Individual Variation in DNA Methylation of IFNg and IL4 Over Days J. S. Kuriakose, D. Torrone, K. Gauvey-Kern, S. Hsu, M. Niedzwiecki, H. Jiang, F. Perera, R. L. Miller; Columbia University College of Physicians & Surgeons, New York, NY. RATIONALE: The mechanisms linking environmental exposure with asthma are complex and may involve epigenetic regulation of inflammatory genes. Using buccal cells as a sentinel population representative of changes in airways, we hypothesized epigenetic marks in allergic inflammatory genes in buccal DNA can vary over several days. METHODS: Buccal DNA was collected twice, 4-7 days apart from 8 nonsmoking adults and 4 children, from the Columbia Center for Children’s Environmental Health cohort. Methylation analysis using bisulfite conversion followed by pyrosequencing was performed on select CpG sites within the proximal promoter of the IFNg gene and the proximal promoter and second intron of the IL4 gene. RESULTS: Percent cytosine methylation (%5 mC) of IFNg ranged from 5979% for CpG-186 and 72-91% for CpG-295. Within the IL4 proximal promoter, %5 mC ranged from 56-100% for CpG-144, CpG-113, CpG-60, and CpG-12. Within the IL4 second intron, %5 mC ranged from 66-100% for CpG+1018, CpG+1064, CpG +969, CpG+1082, CpG-113, CpG+997, CpG+959, CpG+1044 and CpG+1001. After 4-7 days: %5 mC of IL4 at CpG-60 was decreased (mean difference (MD)5 4.9%5 mC, P50.045; Wilcoxon Rank Sum); %5 mC of IL4 at CpG+1082 was decreased (MD 5 3.1 %5 mC; P50.038). The %5 mC of IFNg at CpG-186 and CpG-295 increased (MD55%5 mC and 9.6%5 mC; P50.06 and 0.18, respectively). CONCLUSIONS: Individual buccal DNA methylation changes were found in CpG sites in the proximal promoter of IFNg, IL4, and second intron of IL4 after several days. Pilot data suggest DNA methylation may be dynamic and influenced by recent environmental exposures.
J ALLERGY CLIN IMMUNOL FEBRUARY 2011
Exploring The Novel Il-17-producing Cd4+TH2 Memory Cell Subset In Clinically Defined Asthmatic Patients. B. Uygungil1, J. A. Bernstein2, Y. Wang1; 1Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, 2University of Cincinnati, Cincinnati, OH. RATIONALE: In prior studies, we identified a subset of circulating human CD4+T cells expressing CRTH2, the prostaglandin D2 receptor, and CCR6 that are IL-17-TH2 memory cells featuring concurrent TH17 and TH2 cytokine production. In a mouse model of allergic lung disease, we showed that antigen specific IL-17-producing TH2 memory cells induced profound influx of heterogeneous inflammatory leukocytes and exacerbated pathology, suggesting a potential role of IL-17-TH2 memory cells in promoting the chronic asthma. Based on these mouse and human studies, we hypothesize that the occurrence of IL-17-TH2 memory cells in blood will be associated with the symptoms of clinically well-defined asthmatic patients. METHODS: A cross-sectional study is being conducted on adult asthma _ 12% patients 18-65 years of age with evidence of airway obstruction and > change in FEV1 post-bronchodilators. Atopy is defined as positive skin prick tests to two or more aeroallergens. The frequency of IL-17-TH2 memory cells in peripheral blood is examined using multicolor immunofluorescence analysis. RESULTS: The average age of atopic asthma patients analyzed thus far was 49 years and 75% were female. The frequency of IL-17-TH2 memory cells within the total CD4+TH2 memory pool were higher in atopic asthma patients (33% 69.7; n532) compared to a group of non-allergic, non-asthmatic donors (16% 67.6; n516). CONCLUSIONS: These preliminary results reveal that atopic asthma patients have greater IL-17-TH2 memory cells than normal controls. Larger numbers of non-atopic asthma and atopic non-asthma patient groups will be included in this ongoing analysis to elucidate whether this marker helps define asthma control on a cellular level.
3
4
Persistent High FeNO Phenotype in Asthma I. O. Agache, C. Ciobanu; Transylvania University Brasov, Faculty of Medicine, Brasov, ROMANIA. RATIONALE: Exhaled NO (FeNO) was validated as a marker for eosinophilc inflammation and for predicting response to inhaled corticosteroids (ICS), but FeNO use for tailoring treatment gave conflicting results. The implications of the persistent high FeNO phenotype in asthma have not been yet evaluated. METHODS: FeNO was measured serially for at least 4 times at 3-4 months interval in 91children (5-16 years old) and 165 adult asthmatics treated with an ICS 6LABA/LTRA at a dosage recommended by GINA guidelines to achieve asthma control. Subjects with persistent high FeNO (above 45 ppb at all the serial measurements done) were compared with asthmatics with low FeNO (<25 ppb) for male sex, obesity, atopy, allergen exposure, moderate/severe persistent rhinitis, mean ACT score, severe asthma exacerbations, persistent low FEV1 (100 ml/year). Statistics by Chi test. RESULTS:9(9.89%) children and 31(18.79%) adults had persistent high FeNO. In children obesity (p50.0062) and in adults atopy (p50.0066) and low ACT score (p50.0000) were significantly higher in subjects with persistent high FeNO phenotype. Both in children and in adults the incidences of persistent low FEV1 (children p50.0109, adults p50.0438) and of the fast FEV1 decline (children p50.0000, adults p50.0011) were significant. There was no impact on the incidence of severe asthma exacerbations. CONCLUSIONS: Persistent high FeNO has distinct phenotypic traits in asthmatic children compared with adults. Both in children and in adults persistent high FeNO is associated with poor lung function and in adults with low ACT score.