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Assessment of the Influence of Asthma Status on Serotype-Specific Antibody Response to Pneumococcal Polysaccharide Antigens
S82 Abstracts
303
SUNDAY
Assessment of the Influence of Asthma Status on SerotypeSpecific Antibody Response to Pneumococcal Polysaccharide Antigens J. A. Jung1, H. Kita1, R. Mann1, C. Tsigrelis2, L. M. Baddour2, R. M. Jacobson1, T. G. Boyce1, Y. J. Juhn1; 1Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, MN, 2Department of Internal Medicine, Mayo Clinic, Rochester, MN. RATIONALE: Asthma has been reported to be associated with an increased risk of invasive pneumococcal disease (IPD). We compared serotype-specific antibody responses to pneumococcal polysaccharide antigens between individuals with and without asthma. METHODS: A cross-sectional study was conducted for 16 subjects with asthma and 14 subjects without asthma from the community of Rochester, Minnesota. Asthma was determined by predetermined criteria based on comprehensive medical record reviews. Serotype-specific antibody to 23 pneumococcal polysaccharide antigens was measured by ELISA and positivity was considered higher than 1.3 mg/mL. IFN-g, IL-5, and IL-13 from peripheral blood mononuclear cells cultured with house dust mite was measured. RESULTS: Of the 30 subjects, 16 (53%) were male, 21 (70%) were Caucasians, and the median age was 26 years old. The median number of positive serotype-specific antibodies for asthmatics and non-asthmatics was 9 (39%, 9/23) and 16 (70%, 16/23), respectively (p 5 0.041). There was an inverse relationship between the ratio of log-transformed IL-5/ IFN-g and the number of positive serotype-specific antibodies (g 5 - 0.37, p 5 0.043). As potential covariates and confounders, history of pneumococcal vaccination (p 5 0.84), having a high-risk condition for IPD (p 5 0.83), and taking asthma medications including inhaled corticosteroid (p 5 0.61) were not associated with the number of positive serotypespecific antibodies. CONCLUSIONS: Asthmatics have significantly poorer serotype-specific antibody responses to pneumococcal polysaccharide antigens than nonasthmatics. As a potential mediator, T-helper 2-predominant response appears to be associated with the poorer humoral immune response in asthmatics. These findings might be a mechanism underlying an increased risk of IPD in asthmatics.
304
Inclusion of Rhinovirus Wheezing History in Early Life Improves the Sensitivity of the Modified Asthma Predictive Index (mAPI) D. J. Jackson, T. W. Guilbert, M. D. Evans, R. E. Gangnon, K. A. Roberg, E. L. Anderson, T. E. Pappas, C. J. Tisler, D. F. DaSilva, L. E. P. Salazar, J. E. Gern, R. F. Lemanske, Jr; University of Wisconsin, Madison, WI. RATIONALE: Many children wheeze during early life, but not all children who wheeze subsequently develop asthma. The predictive value of the modified Asthma Predictive Index (mAPI) has not been established. METHODS: 259 children were followed prospectively from birth to 6 years in the COAST (Childhood Origins of ASThma) study. A positive mAPI was defined as 4 wheezing episodes in the previous year and either 1 major criteria (parental asthma, atopic dermatitis, or allergic sensitization to aeroallergen) or 2 minor criteria (allergic sensitization to food, blood eosinophils 4%, or wheezing unrelated to colds). The mAPI was then altered to replace 4 wheezing episodes in the previous year with 1 rhinovirus (RV) wheezing illness in the previous year. The predictive value of these two indices for current asthma at age 6 years was assessed. RESULTS: Asthma was diagnosed in 28% (73 of 259) of COAST children at age 6 years. A positive mAPI at any time during the first 3 years of life was 30.1% sensitive and 98.4% specific for the diagnosis of asthma at age 6 years. When the mAPI was altered to include RV wheezing rather than 4 episodes of wheezing, the sensitivity increased to 58.9%, while the specificity decreased to 86.6%. CONCLUSIONS: The mAPI is a specific, but not sensitive, predictor of year 6 asthma in high-risk children. Diagnosis of 1 RV wheezing illness during the first 3 years of life significantly increases the sensitivity of the index while maintaining relatively high specificity.
J ALLERGY CLIN IMMUNOL FEBRUARY 2009
305
Silent Airflow Obstruction and Air Trapping in Children Admitted to the Hospital with Asthma R. Morton, V. Kailasnath, B. Vancleave, N. Eid; University of Louisville and Kosair Children’s Hospital, Louisville, KY. RATIONALE: Lung function tests are often underutilized in assessing safe discharge criteria for children with status asthmaticus. We hypothesized that children being discharged from the hospital have persistent airflow obstruction and air trapping on lung functions not apparent from physical examination alone. METHODS: We retrospectively reviewed pulmonary function tests (PFTs) between April 2005 and July 2007 of children admitted to Kosair Children’s Hospital with acute asthma. Patients performed pulmonary function testing when the treating physician felt the patient was ready for discharge based on clinical improvement and the respiratory assessment score. Patients (ages 6-17, mean 12 years) were included if they had an admitting diagnosis of asthma and were able to perform lung functions (both spirometry pre and post bronchodilator and lung volumes). Lung functions were excluded if they showed poor effort based on flowvolume loop or a purely restrictive pattern in airflows. RESULTS: We reviewed one hundred sixty-one lung function tests. Twenty-five percent of patients showed moderate airflow obstruction (FEV1 < 70%). We observed moderate air trapping (RV/TLC > 30) in 40% patients, while 14% patients showed severe airtrapping (RV/TLC > 40). We observed no correlation between the FEV1% and RV/TLC ratios. CONCLUSIONS: We found children admitted with asthma and being discharged home to have moderate airflow obstruction and air trapping on PFTs, which was not apparent on physical assessment. We suggest strict adherence to the NAEPP guidelines on performing spirometry prior to a safe home discharge.
306
Association of CD23 Polymorphisms with Allergy S. Handoyo, J. Meng, L. Rosenwasser; Children’s Mercy Hospital, Kansas City, MO. RATIONALE: CD23 is important in antigen presentation, regulation of IgE synthesis and proinflammatory process in allergy. An R62 W SNP of CD23 was demonstrated to cause a functional change in our previous study. TagSNPs were genotyped to comprehensively understand the genomic region and multiple genetic polymorphisms of CD23 associated with allergy. METHODS: Nine tagSNPs, selected based on Multi-Pop-TagSelect Algorithm for multiple populations, were genotyped in allergic and control subjects. These genetic polymorphisms and the corresponding haplotypes were examined for association with allergy, total plasma IgE, plasma soluble CD23 and cell proliferation of PBMC in response to antigens using logistic and multi-variant linear regression approaches. RESULTS: In our Caucasian population, a haplotype GGG in a LD block (rs28364072, rs12984649 and rs2277989) around 3’ UTR as well as the genotype GG in rs2277989 was potentially associated with lower risk of allergy. Allele G in SNP rs1298464, allele G in SNP rs2277989 and allele A in SNP rs2287867 were significantly associated with lower level of total plasma IgE as well (p 5 0.0016; p 5 0.0033; p 5 0.025). Genotype GG in rs28364072 was associated with lower total plasma IgE in Asian population at close to significance level (p 5 0.08). Furthermore, allele C in SNP rs7249360 and allele C in SNP rs4804221 close to promoter were significantly associated with higher plasma soluble CD23 in Caucasian and combined population. CONCLUSIONS: Multiple genomic regions and multiple polymorphisms of CD23 were associated with allergy related phenotypes suggesting the possible contribution of these genetic variations to allergy.
303
SUNDAY
Assessment of the Influence of Asthma Status on SerotypeSpecific Antibody Response to Pneumococcal Polysaccharide Antigens J. A. Jung1, H. Kita1, R. Mann1, C. Tsigrelis2, L. M. Baddour2, R. M. Jacobson1, T. G. Boyce1, Y. J. Juhn1; 1Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, MN, 2Department of Internal Medicine, Mayo Clinic, Rochester, MN. RATIONALE: Asthma has been reported to be associated with an increased risk of invasive pneumococcal disease (IPD). We compared serotype-specific antibody responses to pneumococcal polysaccharide antigens between individuals with and without asthma. METHODS: A cross-sectional study was conducted for 16 subjects with asthma and 14 subjects without asthma from the community of Rochester, Minnesota. Asthma was determined by predetermined criteria based on comprehensive medical record reviews. Serotype-specific antibody to 23 pneumococcal polysaccharide antigens was measured by ELISA and positivity was considered higher than 1.3 mg/mL. IFN-g, IL-5, and IL-13 from peripheral blood mononuclear cells cultured with house dust mite was measured. RESULTS: Of the 30 subjects, 16 (53%) were male, 21 (70%) were Caucasians, and the median age was 26 years old. The median number of positive serotype-specific antibodies for asthmatics and non-asthmatics was 9 (39%, 9/23) and 16 (70%, 16/23), respectively (p 5 0.041). There was an inverse relationship between the ratio of log-transformed IL-5/ IFN-g and the number of positive serotype-specific antibodies (g 5 - 0.37, p 5 0.043). As potential covariates and confounders, history of pneumococcal vaccination (p 5 0.84), having a high-risk condition for IPD (p 5 0.83), and taking asthma medications including inhaled corticosteroid (p 5 0.61) were not associated with the number of positive serotypespecific antibodies. CONCLUSIONS: Asthmatics have significantly poorer serotype-specific antibody responses to pneumococcal polysaccharide antigens than nonasthmatics. As a potential mediator, T-helper 2-predominant response appears to be associated with the poorer humoral immune response in asthmatics. These findings might be a mechanism underlying an increased risk of IPD in asthmatics.
304
Inclusion of Rhinovirus Wheezing History in Early Life Improves the Sensitivity of the Modified Asthma Predictive Index (mAPI) D. J. Jackson, T. W. Guilbert, M. D. Evans, R. E. Gangnon, K. A. Roberg, E. L. Anderson, T. E. Pappas, C. J. Tisler, D. F. DaSilva, L. E. P. Salazar, J. E. Gern, R. F. Lemanske, Jr; University of Wisconsin, Madison, WI. RATIONALE: Many children wheeze during early life, but not all children who wheeze subsequently develop asthma. The predictive value of the modified Asthma Predictive Index (mAPI) has not been established. METHODS: 259 children were followed prospectively from birth to 6 years in the COAST (Childhood Origins of ASThma) study. A positive mAPI was defined as 4 wheezing episodes in the previous year and either 1 major criteria (parental asthma, atopic dermatitis, or allergic sensitization to aeroallergen) or 2 minor criteria (allergic sensitization to food, blood eosinophils 4%, or wheezing unrelated to colds). The mAPI was then altered to replace 4 wheezing episodes in the previous year with 1 rhinovirus (RV) wheezing illness in the previous year. The predictive value of these two indices for current asthma at age 6 years was assessed. RESULTS: Asthma was diagnosed in 28% (73 of 259) of COAST children at age 6 years. A positive mAPI at any time during the first 3 years of life was 30.1% sensitive and 98.4% specific for the diagnosis of asthma at age 6 years. When the mAPI was altered to include RV wheezing rather than 4 episodes of wheezing, the sensitivity increased to 58.9%, while the specificity decreased to 86.6%. CONCLUSIONS: The mAPI is a specific, but not sensitive, predictor of year 6 asthma in high-risk children. Diagnosis of 1 RV wheezing illness during the first 3 years of life significantly increases the sensitivity of the index while maintaining relatively high specificity.
J ALLERGY CLIN IMMUNOL FEBRUARY 2009
305
Silent Airflow Obstruction and Air Trapping in Children Admitted to the Hospital with Asthma R. Morton, V. Kailasnath, B. Vancleave, N. Eid; University of Louisville and Kosair Children’s Hospital, Louisville, KY. RATIONALE: Lung function tests are often underutilized in assessing safe discharge criteria for children with status asthmaticus. We hypothesized that children being discharged from the hospital have persistent airflow obstruction and air trapping on lung functions not apparent from physical examination alone. METHODS: We retrospectively reviewed pulmonary function tests (PFTs) between April 2005 and July 2007 of children admitted to Kosair Children’s Hospital with acute asthma. Patients performed pulmonary function testing when the treating physician felt the patient was ready for discharge based on clinical improvement and the respiratory assessment score. Patients (ages 6-17, mean 12 years) were included if they had an admitting diagnosis of asthma and were able to perform lung functions (both spirometry pre and post bronchodilator and lung volumes). Lung functions were excluded if they showed poor effort based on flowvolume loop or a purely restrictive pattern in airflows. RESULTS: We reviewed one hundred sixty-one lung function tests. Twenty-five percent of patients showed moderate airflow obstruction (FEV1 < 70%). We observed moderate air trapping (RV/TLC > 30) in 40% patients, while 14% patients showed severe airtrapping (RV/TLC > 40). We observed no correlation between the FEV1% and RV/TLC ratios. CONCLUSIONS: We found children admitted with asthma and being discharged home to have moderate airflow obstruction and air trapping on PFTs, which was not apparent on physical assessment. We suggest strict adherence to the NAEPP guidelines on performing spirometry prior to a safe home discharge.
306
Association of CD23 Polymorphisms with Allergy S. Handoyo, J. Meng, L. Rosenwasser; Children’s Mercy Hospital, Kansas City, MO. RATIONALE: CD23 is important in antigen presentation, regulation of IgE synthesis and proinflammatory process in allergy. An R62 W SNP of CD23 was demonstrated to cause a functional change in our previous study. TagSNPs were genotyped to comprehensively understand the genomic region and multiple genetic polymorphisms of CD23 associated with allergy. METHODS: Nine tagSNPs, selected based on Multi-Pop-TagSelect Algorithm for multiple populations, were genotyped in allergic and control subjects. These genetic polymorphisms and the corresponding haplotypes were examined for association with allergy, total plasma IgE, plasma soluble CD23 and cell proliferation of PBMC in response to antigens using logistic and multi-variant linear regression approaches. RESULTS: In our Caucasian population, a haplotype GGG in a LD block (rs28364072, rs12984649 and rs2277989) around 3’ UTR as well as the genotype GG in rs2277989 was potentially associated with lower risk of allergy. Allele G in SNP rs1298464, allele G in SNP rs2277989 and allele A in SNP rs2287867 were significantly associated with lower level of total plasma IgE as well (p 5 0.0016; p 5 0.0033; p 5 0.025). Genotype GG in rs28364072 was associated with lower total plasma IgE in Asian population at close to significance level (p 5 0.08). Furthermore, allele C in SNP rs7249360 and allele C in SNP rs4804221 close to promoter were significantly associated with higher plasma soluble CD23 in Caucasian and combined population. CONCLUSIONS: Multiple genomic regions and multiple polymorphisms of CD23 were associated with allergy related phenotypes suggesting the possible contribution of these genetic variations to allergy.