Early Life Exposure to Maternal Stress is Associated with Asthma

and 691 babies (4.9%) had birthweight <2500 g. RR (95% CI) of an asthmatic mother with premature child for GA<28 wks, <32 wks and <37 wks were 2.77 (1.31-5.87), 3.04 (2.03-4.56) and 1.13 (0.92-1.38) respectively, compared to non-asthmatic mothers. RR for asthmatic mothers having a post-term child (>42 wks GA) was 0.63 (0.41-0.98). RR of an asthmatic mother having a low birthweight child <1000g, <1500g, <2000g, and <2500g were 3.8 (1.81-7.96), 3.23 (2.1-4.97), 1.86 (1.33-2.59) and 1.29 (1.04-1.6) respectively. CONCLUSIONS: Maternal asthma is a risk factor for prematurity and low birthweight. The impact of atopy remains to be determined. Funding: Allergen, National Training Program in Allergy and Asthma, CIHR Early Life Exposure to Maternal Stress is Associated with Asthma A. L. Kozyrskyj1,2, P. McGrath3, B. MacNeil4, X. Mai1,5, A. B. Becker2, K. T. HayGlass5; 1Faculty of Pharmacy, University of Manitoba, Winnipeg, MB, CANADA, 2Pediatrics & Child Health, University of Manitoba, Winnipeg, MB, CANADA, 3Psychology, Dalhousie University, Halifax, NS, CANADA, 4School of Medical Rehabilitation, University of Manitoba, Winnipeg, MB, CANADA, 5Immunology, University of Manitoba, Winnipeg, MB, CANADA. RATIONALE: To determine whether maternal stress in early life is associated with the development of asthma at age 7 in a birth cohort of children. METHODS: Using Manitoba’s health care database records, asthma at age 7 years was identified in a 1995 birth cohort, on the basis of health care visits for asthma (ICD9 code 493) or receipt of asthma prescription drugs. Maternal stress was defined as the presence of physician visits for depression/anxiety or prescriptions for antidepressants/anxiolytics. The likelihood (odds ratio, OR) of asthma, adjusted for child sex, urban/rural location, health care use, household income, number of siblings and maternal history of asthma, was determined for maternal stress in the first year of life. Analyses were repeated for cumulative exposure to maternal stress at child age 4 and 7 years. RESULTS: 13980 children were born in Manitoba in 1995. 19% of children were exposed to maternal stress during the first year of life. Independent of other asthma risk factors, this early life exposure to stress increased the likelihood of asthma (OR=1.2, 95%CI; 1.02-1.41). 11% of children were re-exposed to maternal stress by age 7 and 8% were reexposed at age 4 and 7 years. Re-exposure to maternal stress by age 7 increased the likelihood of asthma (OR=1.3, 95%CI; 1.06-1.57) and continuous exposure further increased the likelihood of asthma (OR=1.4, 95%CI; 1.10-1.69). CONCLUSIONS: Early life exposure to maternal stress is associated with the development of asthma. This risk is further increased with repeated exposure to maternal stress. Funding: AllerGen NCE Inc

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Acetaminophen (APAP) Use Predicts Physician Diagnosis Of Asthma: A Multivariate Analysis of the NHANES III Database G. P. Geba1, R. R. Arons2; 1Mailman School of Public Health, Environmental Health Sciences, Columbia University, New York, NY, 2Mailman School of Public Health, Sociomedical Sciences, Columbia University, New York, NY. RATIONALE: Previous studies associated APAP use and asthma in US nurses (30-55 years old), and residents of south London (aged 16-49). We analyzed a population-based, cross-sectional US survey, to determine whether APAP use predicted physician-diagnosis of asthma.

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METHODS: NHANES III Household components of adult (>16 yrs of age), youth (ages 2 months to 16 years), and examination databases were merged using SAS. Descriptive statistics and multivariate logistic regression were performed with SUDAAN, to account for complex, multistage sampling design. Factors were identified by bivariate logistic regression. To characterize effect of APAP on asthma, controlling for independent predictors, multivariate logistic regression was performed. APAP doseresponse and effect of other types of analgesics were determined. RESULTS: Sex, race, age and urban dwelling did not affect odds of asthma. History of hay fever, sinusitis, colds, having smoked cigarettes and any use of APAP (unadjusted ORs: 5.27, 1.91, 1.51, 1.38, 1.44, respectively), but not ibuprofen or aspirin, significantly increased asthma odds. APAP increased odds of asthma even when combined with other analgesics. Controlling for other covariates, odds of asthma increased 32% overall in adults who used APAP [adjusted OR 1.32 (95% CI: 1.081.62)]. Odds increased by dose, peaking at use of >14-28 times per month (unadjusted OR: 3.49; 95% CI: 2.69-5.82); controlling for other factors, nearly doubling odds of asthma (adjusted OR: 1.90; 95%CI: 1.08-3.35). CONCLUSIONS: This analysis of NHANES III demonstrated a doserelated increase in odds of asthma with APAP, but not other analgesics. Guidelines for APAP use in adults and children may require reassessment. The Major Allergen from Peanut, Ara h 1, is a Ligand of DC-SIGN W. G. Shreffler1, Z. Charlop-Powers1, R. R. Castro1, Z. Y. Kucuk1, A. W. Burks2, H. A. Sampson1; 1Pediatrics, Division of Allergy & Immunology, Mount Sinai School of Medicine, New York, NY, 2Department of Pediatrics, Division of Allergy/ Immunology, Duke University, Durham, NC. RATIONALE: The frequency of peanut as a food allergen suggests that it may have Th2 adjuvant activity. The C-type lectin receptor, DC-SIGN, has been implicated as a pattern recognition receptor that primes dendritic cells to promote Th2 responses. We hypothesized that peanut allergens may interact with DC-SIGN. METHODS: We constructed a DC-SIGN-Fc fusion protein containing the extracellular domain of DC-SIGN including the carbohydrate recognition domain. Precipitation experiments were performed from soluble peanut extract in the presence or absence of calcium. Peanut protein specifically bound was subjected to analysis by immunoblotting and digestion/ mass spectrometry analysis. Direct ELISA using DC-SIGN-Fc was also performed. Monocyte-derived DC were stimulated with whole peanut antigen, purified Ara h1 and controls, and assessed for activation/ maturation by expression of HLA-DR and co-stimulatory molecules as well as the ability to stimulate naïve T cells to alloantigen. RESULTS: DC-SIGN specifically bound only to a 65 kD protein from peanut extract in a calcium-dependent manner. There was no precipitation of proteins from chemically deglycosylated peanut extract. Immunoblotting with anti-Ara h1 mAb was positive. MS analysis confirmed that the DC-SIGN ligand from peanut was Ara h1. ELISA results confirmed calcium-dependent interaction of DC-SIGN-Fc but not control Fc protein with whole peanut antigen and purified Ara h1. Ara h1 activated human DCs as measured by phenotype and T cell stimulation. CONCLUSIONS: Arah1 is a ligand for DC-SIGN and may play a role in differentiating DCs to promote Th2 responses to peanut allergen. Funding: Mount Sinai School of Medicine

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Abstracts S87

J ALLERGY CLIN IMMUNOL VOLUME 117, NUMBER 2