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Dog ownership is associated with less wheezing among high-risk infants during the first year of life
S136 Abstracts
Investigating IgE Cross-reactive Antibody Responses in Invertebrates: Use of Recombinant Tropomyosin From Cockroach and Ascaris lumbricoides A. B. R. Santos1, V. S. F. Sales2, V. P. L. Ferriani3, M. D. Chapman4, L. K. Arruda1; 1Internal Medicine, School of Medicine of Ribeirão Preto University of São Paulo, Ribeirão Preto, BRAZIL, 2Pharmacology, Federal University of Rio Grande do Norte, Natal, BRAZIL, 3Pediatrics, School of Medicine of Ribeirão Preto - University of São Paulo, Ribeirão Preto, BRAZIL, 4Indoor Biotechnologies Inc, Charlottesville, VA. RATIONALE: We have previously shown that infection with A. lumbricoides is an important risk factor for wheezing in children living in Brazil. We aimed to use recombinant tropomyosins to investigate IgE antibody responses to Ascaris and cockroach. METHODS: cDNA coding for A. lumbricoides tropomyosin was subcloned into pPIC-9 vector and expression of the recombinant protein was carried out in the Pichia pastoris system. Recombinant tropomyosins from A. lumbricoides and cockroach were used in chimeric ELISA to quantitate specific IgE antibodies in panels of sera from 137 children living in a parasite-endemic area, and 188 patients with asthma and/or rhinitis allergic to cockroach from our clinic. RESULTS: In children from a parasite-endemic area, IgE to tropomyosin was found in 99/137 (72.2 %) of sera; of those, 57 (41.6%) had IgE to both Ascaris and cockroach tropomyosin. Geometric mean (GM) levels of IgE to Ascaris and cockroach tropomyosin were 7.5 IU/mL and 8.1 IU/mL, respectively. There was a significant correlation of levels of IgE to A. lumbricoides and cockroach tropomyosin (r = 0.7, p < 0.0001). Among cockroach allergic patients, presence of IgE to tropomyosin was found in 79/188 (42%), and of those, 48/188 (25.5%) presented IgE to both Ascaris and cockroach tropomyosin, with GM levels of 2.56 UI/mL and 5.4 UI/mL , respectively. There was also a significant correlation of levels of IgE antibodies to both tropomyosins (r = 0.58, p < 0.0001). CONCLUSION: Tropomyosins from invertebrates are important IgEbinding proteins. Recombinant tropomyosins could be used to investigate IgE antibody responses to Ascaris and cockroach. Funding: FAPESP, CNPq
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SUNDAY
Patterns of Respiratory Viral Infections Correspond Closely With Early Childhood Wheezing Phenotypes T. E. Pappas1, K. T. Sullivan Dillie1, E. L. Anderson1, D. F. DaSilva1, M. D. Evans2, L. E. Pleiss1, K. A. Roberg1, C. J. Tisler1, J. E. Gern3, R. F. Lemanske, Jr.3; 1Department of Pediatrics, University of Wisconsin Madison, Madison, WI, 2Biostatistics and Medical Informatics, University of Wisconsin - Madison, Madison, WI, 3Department of Medicine, University of Wisconsin - Madison, Madison, WI. RATIONALE: Viral infections clearly cause acute wheezing in infancy, but their role in development of recurrent wheezing and asthma remains controversial. METHODS: To explore the relationship between specific viral infections and development of early childhood wheezing, nasal wash specimens were collected for symptomatic respiratory infections as part of the Childhood Origins of ASThma (COAST) study, and analyzed for common respiratory pathogens. At three years, children were categorized into four wheezing phenotypes: infantile (present between 0-2 years of age), recurrent (persistent between 0-3 years of age), late onset (present for the first time in year 2 or 3) and never wheezed. RESULTS: The most frequent infection isolated during each of the first 3 years was rhinovirus (RV). This was true for all wheezing phenotypes. Respiratory syncitial virus (RSV) was next most common, although RSV and parainfluenza viruses were isolated with similar frequency in year three. Recurrent and infantile wheezers had a greater number of infections during the first year (3.18 versus 1.44 in late-onset and never wheezed groups, p<0.0001), and had significantly fewer symptomatic infections afterwards. Infections in the second year were more common in recurrent and late-onset wheezers compared to the other children (3.20 versus 1.70, p<0.0001), and the same pattern was noted in year three (2.96 versus 0.98, p<0.0001). These trends were driven mainly by differences in number of RV infections.
543
J ALLERGY CLIN IMMUNOL FEBRUARY 2005
CONCLUSION: Wheezing in early childhood is associated with increased numbers of moderate to severe viral respiratory tract infections, especially RV. The timing of these infections closely corresponds to development of particular wheezing phenotypes. Funding: NIH grants M01 RR03186, R01 HL61879, and P01 HL70831 Dog Ownership Is Associated With Less Wheezing Among High-Risk Infants During the First Year of Life H. K. Kalra1,2, P. Campo1, D. I. Bernstein1, L. Levin3, R. Olds1, T. Reponin3, Z. L. Lummus1, S. H. Cho3, M. Villareal1, G. M. LeMasters3; 1Internal Medicine, University of Cincinnati, Cincinnati, OH, 2Cincinnati Children’s Hospital, Cincinnati, OH, 3Environmental Health, University of Cincinnati, Cincinnati, OH. RATIONALE: Pet ownership has been reported to influence allergic sensitization and asthma in childhood. METHODS: In a birth cohort of 881 one year old infants born to atopic parents participating in the Cincinnati Children Allergy and Air Pollution Study, we collected house dust samples from the living area of 367 infants. Der f 1, Fel d1, Bla g1 were analyzed by monoclonal ELISA, dog and Alternaria antigen by competitive inhibition assay, and endotoxin by Limulus assay. Clinical assessments and skin prick testing were performed with 15 aeroallergens, milk and egg. RESULTS: Geometric mean levels/g of dust sample were: 0.32 g Der f1; 2.15 g Fel d1; 0.34 IU Bla g1; 17.4 g of dog allergen & 39.4 g Alternaria. Wheezing (≥2 episodes in past 12 months) was less likely if dogs were present in the home (40% of households); prevalence was 18%, 26% if a dog was present versus absent (X2 = 3.5, p=0.06). Although dog ownership was significantly and positively associated with the highest level of endotoxin or > 140 EU/mg dust (X2 = 4.8; p=0.03), logistic regression showed that high (>140 EU/mg) endotoxin exposure (versus < 140), controlling for the presence of dog was positively but non-significantly related to wheezing [OR=1.4 (95% CI=0.8, 2.4)]; prevalence was 26% and 21%, respectively. No significant relationship was found between level of endotoxin exposure or pet ownership on prevalence of cutaneous reactivity to aeroallergens. CONCLUSION: Exposure to dog is associated with less wheezing during the first year of life. Funding: NIEHS 1-R01-ES11170-04
544
Stability of Epinephrine Over Five Months at Four Different Non-Optimal Storage Conditions M. M. Rawas-Qalaji1, E. R. Simons2, K. J. Simons1,2; 1Faculty of Pharmacy, University of Manitoba, Winnipeg, MB, CANADA, 2Pediatrics and Child Health, University of Manitoba, Winnipeg, MB, CANADA. RATIONALE: Epinephrine is the drug of choice in the first-aid treatment of anaphylaxis. When epinephrine auto-injectors are unavailable or unaffordable, outpatients are sometimes supplied with epinephrine in prefilled syringes. This practice raises concern about epinephrine stability. We hypothesized that epinephrine stability might be a particular concern under conditions of high ambient temperature and different humidity and light conditions. METHODS: Pre-filled epinephrine syringes (PFES) with a 0.3 mg dose (n=40) were stored at 38°C for 5 months, with 10 PFES in each of four different standardized storage conditions: dark and light at 15% (low) humidity (LH) and dark and light at 95% (high) humidity (HH). Duplicate PFES were removed monthly from each environment and stored frozen until analyzed for epinephrine by HPLC-UV. The results were calculated as % epinephrine dose loss at p<0.05. RESULTS: At 38°C in HH, epinephrine doses were within USP compendial limits at 1, 2 and 3 months, but mean±SEM epinephrine loss was 11.8%±2.6% at 4 months and 13.2±2.6% at 5 months. However, in LH, epinephrine doses were within USP limits at only 1 and 2 months, while epinephrine loss was 36.0%±3.7% at 3 months, 41.9%±7.7% at 4 months, and 58.8%±7.4% at 5 months. Dark and light conditions had no effect. CONCLUSIONS: Storage of PFES at high temperature plus low humidity appeared to compromise stability more than high temperature plus
545
Investigating IgE Cross-reactive Antibody Responses in Invertebrates: Use of Recombinant Tropomyosin From Cockroach and Ascaris lumbricoides A. B. R. Santos1, V. S. F. Sales2, V. P. L. Ferriani3, M. D. Chapman4, L. K. Arruda1; 1Internal Medicine, School of Medicine of Ribeirão Preto University of São Paulo, Ribeirão Preto, BRAZIL, 2Pharmacology, Federal University of Rio Grande do Norte, Natal, BRAZIL, 3Pediatrics, School of Medicine of Ribeirão Preto - University of São Paulo, Ribeirão Preto, BRAZIL, 4Indoor Biotechnologies Inc, Charlottesville, VA. RATIONALE: We have previously shown that infection with A. lumbricoides is an important risk factor for wheezing in children living in Brazil. We aimed to use recombinant tropomyosins to investigate IgE antibody responses to Ascaris and cockroach. METHODS: cDNA coding for A. lumbricoides tropomyosin was subcloned into pPIC-9 vector and expression of the recombinant protein was carried out in the Pichia pastoris system. Recombinant tropomyosins from A. lumbricoides and cockroach were used in chimeric ELISA to quantitate specific IgE antibodies in panels of sera from 137 children living in a parasite-endemic area, and 188 patients with asthma and/or rhinitis allergic to cockroach from our clinic. RESULTS: In children from a parasite-endemic area, IgE to tropomyosin was found in 99/137 (72.2 %) of sera; of those, 57 (41.6%) had IgE to both Ascaris and cockroach tropomyosin. Geometric mean (GM) levels of IgE to Ascaris and cockroach tropomyosin were 7.5 IU/mL and 8.1 IU/mL, respectively. There was a significant correlation of levels of IgE to A. lumbricoides and cockroach tropomyosin (r = 0.7, p < 0.0001). Among cockroach allergic patients, presence of IgE to tropomyosin was found in 79/188 (42%), and of those, 48/188 (25.5%) presented IgE to both Ascaris and cockroach tropomyosin, with GM levels of 2.56 UI/mL and 5.4 UI/mL , respectively. There was also a significant correlation of levels of IgE antibodies to both tropomyosins (r = 0.58, p < 0.0001). CONCLUSION: Tropomyosins from invertebrates are important IgEbinding proteins. Recombinant tropomyosins could be used to investigate IgE antibody responses to Ascaris and cockroach. Funding: FAPESP, CNPq
542
SUNDAY
Patterns of Respiratory Viral Infections Correspond Closely With Early Childhood Wheezing Phenotypes T. E. Pappas1, K. T. Sullivan Dillie1, E. L. Anderson1, D. F. DaSilva1, M. D. Evans2, L. E. Pleiss1, K. A. Roberg1, C. J. Tisler1, J. E. Gern3, R. F. Lemanske, Jr.3; 1Department of Pediatrics, University of Wisconsin Madison, Madison, WI, 2Biostatistics and Medical Informatics, University of Wisconsin - Madison, Madison, WI, 3Department of Medicine, University of Wisconsin - Madison, Madison, WI. RATIONALE: Viral infections clearly cause acute wheezing in infancy, but their role in development of recurrent wheezing and asthma remains controversial. METHODS: To explore the relationship between specific viral infections and development of early childhood wheezing, nasal wash specimens were collected for symptomatic respiratory infections as part of the Childhood Origins of ASThma (COAST) study, and analyzed for common respiratory pathogens. At three years, children were categorized into four wheezing phenotypes: infantile (present between 0-2 years of age), recurrent (persistent between 0-3 years of age), late onset (present for the first time in year 2 or 3) and never wheezed. RESULTS: The most frequent infection isolated during each of the first 3 years was rhinovirus (RV). This was true for all wheezing phenotypes. Respiratory syncitial virus (RSV) was next most common, although RSV and parainfluenza viruses were isolated with similar frequency in year three. Recurrent and infantile wheezers had a greater number of infections during the first year (3.18 versus 1.44 in late-onset and never wheezed groups, p<0.0001), and had significantly fewer symptomatic infections afterwards. Infections in the second year were more common in recurrent and late-onset wheezers compared to the other children (3.20 versus 1.70, p<0.0001), and the same pattern was noted in year three (2.96 versus 0.98, p<0.0001). These trends were driven mainly by differences in number of RV infections.
543
J ALLERGY CLIN IMMUNOL FEBRUARY 2005
CONCLUSION: Wheezing in early childhood is associated with increased numbers of moderate to severe viral respiratory tract infections, especially RV. The timing of these infections closely corresponds to development of particular wheezing phenotypes. Funding: NIH grants M01 RR03186, R01 HL61879, and P01 HL70831 Dog Ownership Is Associated With Less Wheezing Among High-Risk Infants During the First Year of Life H. K. Kalra1,2, P. Campo1, D. I. Bernstein1, L. Levin3, R. Olds1, T. Reponin3, Z. L. Lummus1, S. H. Cho3, M. Villareal1, G. M. LeMasters3; 1Internal Medicine, University of Cincinnati, Cincinnati, OH, 2Cincinnati Children’s Hospital, Cincinnati, OH, 3Environmental Health, University of Cincinnati, Cincinnati, OH. RATIONALE: Pet ownership has been reported to influence allergic sensitization and asthma in childhood. METHODS: In a birth cohort of 881 one year old infants born to atopic parents participating in the Cincinnati Children Allergy and Air Pollution Study, we collected house dust samples from the living area of 367 infants. Der f 1, Fel d1, Bla g1 were analyzed by monoclonal ELISA, dog and Alternaria antigen by competitive inhibition assay, and endotoxin by Limulus assay. Clinical assessments and skin prick testing were performed with 15 aeroallergens, milk and egg. RESULTS: Geometric mean levels/g of dust sample were: 0.32 g Der f1; 2.15 g Fel d1; 0.34 IU Bla g1; 17.4 g of dog allergen & 39.4 g Alternaria. Wheezing (≥2 episodes in past 12 months) was less likely if dogs were present in the home (40% of households); prevalence was 18%, 26% if a dog was present versus absent (X2 = 3.5, p=0.06). Although dog ownership was significantly and positively associated with the highest level of endotoxin or > 140 EU/mg dust (X2 = 4.8; p=0.03), logistic regression showed that high (>140 EU/mg) endotoxin exposure (versus < 140), controlling for the presence of dog was positively but non-significantly related to wheezing [OR=1.4 (95% CI=0.8, 2.4)]; prevalence was 26% and 21%, respectively. No significant relationship was found between level of endotoxin exposure or pet ownership on prevalence of cutaneous reactivity to aeroallergens. CONCLUSION: Exposure to dog is associated with less wheezing during the first year of life. Funding: NIEHS 1-R01-ES11170-04
544
Stability of Epinephrine Over Five Months at Four Different Non-Optimal Storage Conditions M. M. Rawas-Qalaji1, E. R. Simons2, K. J. Simons1,2; 1Faculty of Pharmacy, University of Manitoba, Winnipeg, MB, CANADA, 2Pediatrics and Child Health, University of Manitoba, Winnipeg, MB, CANADA. RATIONALE: Epinephrine is the drug of choice in the first-aid treatment of anaphylaxis. When epinephrine auto-injectors are unavailable or unaffordable, outpatients are sometimes supplied with epinephrine in prefilled syringes. This practice raises concern about epinephrine stability. We hypothesized that epinephrine stability might be a particular concern under conditions of high ambient temperature and different humidity and light conditions. METHODS: Pre-filled epinephrine syringes (PFES) with a 0.3 mg dose (n=40) were stored at 38°C for 5 months, with 10 PFES in each of four different standardized storage conditions: dark and light at 15% (low) humidity (LH) and dark and light at 95% (high) humidity (HH). Duplicate PFES were removed monthly from each environment and stored frozen until analyzed for epinephrine by HPLC-UV. The results were calculated as % epinephrine dose loss at p<0.05. RESULTS: At 38°C in HH, epinephrine doses were within USP compendial limits at 1, 2 and 3 months, but mean±SEM epinephrine loss was 11.8%±2.6% at 4 months and 13.2±2.6% at 5 months. However, in LH, epinephrine doses were within USP limits at only 1 and 2 months, while epinephrine loss was 36.0%±3.7% at 3 months, 41.9%±7.7% at 4 months, and 58.8%±7.4% at 5 months. Dark and light conditions had no effect. CONCLUSIONS: Storage of PFES at high temperature plus low humidity appeared to compromise stability more than high temperature plus
545