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Early life mouse allergen exposure and risk of mouse skin test sensitivity
Abstracts S203
J ALLERGY CLIN IMMUNOL VOLUME 115, NUMBER 2
Early Life Mouse Allergen Exposure and Risk of Mouse Skin Test Sensitivity E. C. Matsui1, P. A. Eggleston1, P. Breysse2, J. Curtin-Brosnan1, G. B. Diette3; 1Pediatrics, Johns Hopkins Univ. School Medicine, Baltimore, MD, 2Environmental Health Sciences, Johns Hopkins Univ. Bloomberg School of Public Health, Baltimore, MD, 3Medicine, Johns Hopkins Univ. School Medicine, Baltimore, MD. RATIONALE: It is unknown whether early life exposure to mouse allergen increases or decreases the risk of mouse skin test sensitivity. METHODS: Preschool children (2-6 years old) with asthma (N=112) were recruited from inner-city Baltimore. Children underwent skin prick testing, an environmental questionnaire was administered to assess mouse exposure from prenatal to present time, and dust samples were collected from homes for allergen analysis. RESULTS: Mouse allergen was detected in 98% of kitchens (median [IQR]: 7.4 g/g [0.9-27.8]). Eighty-one percent of caregivers reported mouse infestation at some time during the child’s life (34% reported continuous exposure, and 47% reported intermittent exposure). Sixteen percent were sensitized to mouse. The prevalence of mouse sensitization increased with increasing mouse allergen levels except among children with the highest exposure (14.3, 12.0, 29.2, and 10.7% for children exposed to < 2, 2-7.9, 8-29.9, and ≥ 30.0 g/g, respectively). Similarly, the prevalence rate increased with exposure frequency except for children who were continuously exposed (3.7, 25.5, and 13.2% for rare, intermittent, and continuous exposure, respectively). After adjusting for atopy and gender, the odds of mouse sensitization increased 7% for every 1 g/g increase in mouse allergen up to 30 g/g (95%CI: 0-15%), and decreased 5% for every 1 g/g increase in mouse allergen above 30 g/g (95% CI: 0-9%). CONCLUSIONS: Both moderate and intermittent mouse allergen exposure are risk factors for mouse sensitization, but high level and continuous exposure may be protective. These findings support both a monotonically increasing exposure-sensitization relationship and tolerance at the highest exposure levels. Funding: NIH
810
The Cincinnati Childhood Allergy and Air Pollution Study (CCAAPS): Evaluation of Respiratory Symptoms at Age 1 D. Bernstein 1 , L. Levin 2 , K. Wilson 2 , S. Stanforth 3 , K. Kenner 3 , M. Villareal1, J. Lockey2, G. M. Lemasters2; 1Internal Medicine, University of Cincinnati, Cincinnati, OH, 2Environmental Health, University of Cincinnati, Cincinnati, OH, 3Bernstein Clinical Research Center, Cincinnati, OH. RATIONALE: Although wheezing in the first year is often attributed to viral infections, identifying factors that predict wheezing may help define susceptibility for childhood asthma. METHODS: A birth cohort of 881 infants born to atopic parents were recruited for a 5-year longitudinal study including the following annual assessments: 1) clinical evaluation for wheezing, rhinitis and eczema; 3) skin prick testing (SPT) with 15 aeroallergens, milk and egg 2) home walk-through evaluations with collection of dust samples for indoor allergens; 3) daily measurements of outdoor diesel exhaust particle exposure. Multivariate logistic analysis was performed for 367 subjects who received their SPT at approximately age one andone and whose medical history questionnaires were entered into the data basedatabase. RESULTS: At year 1, maternal cigarette smoking of ≥ 1 pack per day [OR=22 (95% CI=5.5, 91], male gender [OR=2.2 (1.2, 4.2)], attendance at day care [OR=3.0 (1.2, 7.3], number of siblings [OR=2.0 (1.3, 3.0)], and a history of asthma in either parent [OR=1.9 (1.0, 3.6)] were significant predictors of mother’s report of at least 2 episodes of wheezing in the past 12 months. Although 26% of the analyzed subjects exhibited atopy, defined by a positive SPT to any allergenany allergen (14% to an aeroallergen), atopy was not a significant predictor of wheezing. CONCLUSIONS: Exposure to maternal environmental tobacco smoke, siblings and daycare as well as parental histories of asthma and male gender were associated with early wheezing early in life. Funding: NIEHS 1-RO1-ES11170-04
811
Occurrence of Wheezing and Being Overweight in the First Three Years of Life in a Birth Cohort at High Risk for the Development of Asthma/Allergy Z. Zhang1, H. Lai1, K. A. Roberg2, M. D. Evans3, R. E. Gangnon3, E. L. ANDERSON2, J. E. GERN2, R. F. LEMANSKE2; 1Nutritional Sciences, University of Wisconsin-Madison, Madison, WI, 2Pediatrics, University of Wisconsin-Madison, Madison, WI, 3Biostatistics and medical informatics, University of Wisconsin-Madison, Madison, WI. RATIONALE: Recent studies have shown positive associations between asthma and obesity in adults and adolescents; however, these relationships are not defined in young children. Since diet is a common risk factor for both being overweight and having asthma, the objective of this study is to identify the interrelationships among feeding practices, rapid weight-gain and the development of becoming overweight and wheezing in a cohort of children at high risk for asthma from birth to age 3y. METHODS: 275 children enrolled in the Childhood Origin of Asthma (COAST) project were examined using serial questionnaires completed at study visits. RESULTS: Proportionately more children who wheezed in the first year of life were overweight at age 3y compared to those who did not (28.9% vs. 17.5%, p=0.03). In addition to wheezing in the first year (OR=2.5, p=0.03), birth weight > 75th percentile (OR=4.0, p<0.0001) and rapid weight-gain at 0-6 months (OR=5.1, p=0.001) increased risk of being overweight at age 3y. Exclusive breastfeeding > 2 months was marginally protective for being overweight at age 1y (p=0.06), but not for being overweight at age 3 y (p=0.81). Significant risk factors for wheezing in the third year included male gender (OR=2.1, p=0.02), wheezing in the first year (OR=5.2, p<0.0001), exclusive breastfeeding greater than 2 months (OR=2.2, p=0.02) and birth weight < 15th percentile (OR=2.3, p=0.04). CONCLUSIONS: Wheezing during the first year of life increased the risk of being overweight at age 3 years. Exclusive breastfeeding increased the risk of wheezing at age 3 years. Funding: NIH, USDA and American Lung Association
812
MONDAY
Plasma Kallikrein Inhibition: A Viable Method of Treating Laryngeal Edema Secondary to Hereditary Angioedema (HAE) J. Morrison1, M. Cicardi2, L. Baird1, A. Williams1; 1Dyax, Corp., Cambridge, MA, 2Internal Medicine, University of Milan, Milan, ITALY. RATIONALE: HAE is a rare genetic disorder inherited as an autosomal dominant trait, characterized by low serum concentrations of C1 esterase inhibitor (C1-INH). HAE manifests as edema of the face, larynx, oropharynx, abdomen/gastrointestinal tract, external genitalia, or limbs. Acute abdominal attacks can mimic an acute surgical abdomen. Laryngeal edema can cause life-threatening constriction of the airway. Severe facial attacks can progress to laryngeal involvement. DX-88 is a novel kallikrein inhibitor that is being developed for the replacement of C1-INH, which is unavailable in the USA. METHODS: DX-88 has been evaluated in a number of clinical studies in HAE. Patients with laryngeal edema and or severe facial edema are reported upon from these studies. Patients were treated with DX-88 doses of 10-40 mg/m2; one compassionately treated patient received 50 mg of DX-88 had type I hypersensitivity to C1-INH. RESULTS: Of the 14 patients treated for laryngeal edema, 13 reported significant improvement (time to start of resolution varied between 5 and 61 minutes). In seven patients treated for facial or neck edema, six reported the initial resolution of symptoms between 0 and 60 minutes post-dosing; the seventh reported initial resolution by 120 minutes. None these patients required emergency airway management. CONCLUSIONS: These data demonstrate that DX-88 can have a significant clinical impact on treating life-threatening laryngeal edema encountered in many of patients suffering from HAE.
809
J ALLERGY CLIN IMMUNOL VOLUME 115, NUMBER 2
Early Life Mouse Allergen Exposure and Risk of Mouse Skin Test Sensitivity E. C. Matsui1, P. A. Eggleston1, P. Breysse2, J. Curtin-Brosnan1, G. B. Diette3; 1Pediatrics, Johns Hopkins Univ. School Medicine, Baltimore, MD, 2Environmental Health Sciences, Johns Hopkins Univ. Bloomberg School of Public Health, Baltimore, MD, 3Medicine, Johns Hopkins Univ. School Medicine, Baltimore, MD. RATIONALE: It is unknown whether early life exposure to mouse allergen increases or decreases the risk of mouse skin test sensitivity. METHODS: Preschool children (2-6 years old) with asthma (N=112) were recruited from inner-city Baltimore. Children underwent skin prick testing, an environmental questionnaire was administered to assess mouse exposure from prenatal to present time, and dust samples were collected from homes for allergen analysis. RESULTS: Mouse allergen was detected in 98% of kitchens (median [IQR]: 7.4 g/g [0.9-27.8]). Eighty-one percent of caregivers reported mouse infestation at some time during the child’s life (34% reported continuous exposure, and 47% reported intermittent exposure). Sixteen percent were sensitized to mouse. The prevalence of mouse sensitization increased with increasing mouse allergen levels except among children with the highest exposure (14.3, 12.0, 29.2, and 10.7% for children exposed to < 2, 2-7.9, 8-29.9, and ≥ 30.0 g/g, respectively). Similarly, the prevalence rate increased with exposure frequency except for children who were continuously exposed (3.7, 25.5, and 13.2% for rare, intermittent, and continuous exposure, respectively). After adjusting for atopy and gender, the odds of mouse sensitization increased 7% for every 1 g/g increase in mouse allergen up to 30 g/g (95%CI: 0-15%), and decreased 5% for every 1 g/g increase in mouse allergen above 30 g/g (95% CI: 0-9%). CONCLUSIONS: Both moderate and intermittent mouse allergen exposure are risk factors for mouse sensitization, but high level and continuous exposure may be protective. These findings support both a monotonically increasing exposure-sensitization relationship and tolerance at the highest exposure levels. Funding: NIH
810
The Cincinnati Childhood Allergy and Air Pollution Study (CCAAPS): Evaluation of Respiratory Symptoms at Age 1 D. Bernstein 1 , L. Levin 2 , K. Wilson 2 , S. Stanforth 3 , K. Kenner 3 , M. Villareal1, J. Lockey2, G. M. Lemasters2; 1Internal Medicine, University of Cincinnati, Cincinnati, OH, 2Environmental Health, University of Cincinnati, Cincinnati, OH, 3Bernstein Clinical Research Center, Cincinnati, OH. RATIONALE: Although wheezing in the first year is often attributed to viral infections, identifying factors that predict wheezing may help define susceptibility for childhood asthma. METHODS: A birth cohort of 881 infants born to atopic parents were recruited for a 5-year longitudinal study including the following annual assessments: 1) clinical evaluation for wheezing, rhinitis and eczema; 3) skin prick testing (SPT) with 15 aeroallergens, milk and egg 2) home walk-through evaluations with collection of dust samples for indoor allergens; 3) daily measurements of outdoor diesel exhaust particle exposure. Multivariate logistic analysis was performed for 367 subjects who received their SPT at approximately age one andone and whose medical history questionnaires were entered into the data basedatabase. RESULTS: At year 1, maternal cigarette smoking of ≥ 1 pack per day [OR=22 (95% CI=5.5, 91], male gender [OR=2.2 (1.2, 4.2)], attendance at day care [OR=3.0 (1.2, 7.3], number of siblings [OR=2.0 (1.3, 3.0)], and a history of asthma in either parent [OR=1.9 (1.0, 3.6)] were significant predictors of mother’s report of at least 2 episodes of wheezing in the past 12 months. Although 26% of the analyzed subjects exhibited atopy, defined by a positive SPT to any allergenany allergen (14% to an aeroallergen), atopy was not a significant predictor of wheezing. CONCLUSIONS: Exposure to maternal environmental tobacco smoke, siblings and daycare as well as parental histories of asthma and male gender were associated with early wheezing early in life. Funding: NIEHS 1-RO1-ES11170-04
811
Occurrence of Wheezing and Being Overweight in the First Three Years of Life in a Birth Cohort at High Risk for the Development of Asthma/Allergy Z. Zhang1, H. Lai1, K. A. Roberg2, M. D. Evans3, R. E. Gangnon3, E. L. ANDERSON2, J. E. GERN2, R. F. LEMANSKE2; 1Nutritional Sciences, University of Wisconsin-Madison, Madison, WI, 2Pediatrics, University of Wisconsin-Madison, Madison, WI, 3Biostatistics and medical informatics, University of Wisconsin-Madison, Madison, WI. RATIONALE: Recent studies have shown positive associations between asthma and obesity in adults and adolescents; however, these relationships are not defined in young children. Since diet is a common risk factor for both being overweight and having asthma, the objective of this study is to identify the interrelationships among feeding practices, rapid weight-gain and the development of becoming overweight and wheezing in a cohort of children at high risk for asthma from birth to age 3y. METHODS: 275 children enrolled in the Childhood Origin of Asthma (COAST) project were examined using serial questionnaires completed at study visits. RESULTS: Proportionately more children who wheezed in the first year of life were overweight at age 3y compared to those who did not (28.9% vs. 17.5%, p=0.03). In addition to wheezing in the first year (OR=2.5, p=0.03), birth weight > 75th percentile (OR=4.0, p<0.0001) and rapid weight-gain at 0-6 months (OR=5.1, p=0.001) increased risk of being overweight at age 3y. Exclusive breastfeeding > 2 months was marginally protective for being overweight at age 1y (p=0.06), but not for being overweight at age 3 y (p=0.81). Significant risk factors for wheezing in the third year included male gender (OR=2.1, p=0.02), wheezing in the first year (OR=5.2, p<0.0001), exclusive breastfeeding greater than 2 months (OR=2.2, p=0.02) and birth weight < 15th percentile (OR=2.3, p=0.04). CONCLUSIONS: Wheezing during the first year of life increased the risk of being overweight at age 3 years. Exclusive breastfeeding increased the risk of wheezing at age 3 years. Funding: NIH, USDA and American Lung Association
812
MONDAY
Plasma Kallikrein Inhibition: A Viable Method of Treating Laryngeal Edema Secondary to Hereditary Angioedema (HAE) J. Morrison1, M. Cicardi2, L. Baird1, A. Williams1; 1Dyax, Corp., Cambridge, MA, 2Internal Medicine, University of Milan, Milan, ITALY. RATIONALE: HAE is a rare genetic disorder inherited as an autosomal dominant trait, characterized by low serum concentrations of C1 esterase inhibitor (C1-INH). HAE manifests as edema of the face, larynx, oropharynx, abdomen/gastrointestinal tract, external genitalia, or limbs. Acute abdominal attacks can mimic an acute surgical abdomen. Laryngeal edema can cause life-threatening constriction of the airway. Severe facial attacks can progress to laryngeal involvement. DX-88 is a novel kallikrein inhibitor that is being developed for the replacement of C1-INH, which is unavailable in the USA. METHODS: DX-88 has been evaluated in a number of clinical studies in HAE. Patients with laryngeal edema and or severe facial edema are reported upon from these studies. Patients were treated with DX-88 doses of 10-40 mg/m2; one compassionately treated patient received 50 mg of DX-88 had type I hypersensitivity to C1-INH. RESULTS: Of the 14 patients treated for laryngeal edema, 13 reported significant improvement (time to start of resolution varied between 5 and 61 minutes). In seven patients treated for facial or neck edema, six reported the initial resolution of symptoms between 0 and 60 minutes post-dosing; the seventh reported initial resolution by 120 minutes. None these patients required emergency airway management. CONCLUSIONS: These data demonstrate that DX-88 can have a significant clinical impact on treating life-threatening laryngeal edema encountered in many of patients suffering from HAE.
809