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To advance asthma cohort research, we need a method that can use longitudinal data, including when collected at irregular intervals, to model multiple phenotypes of wheeze and identify both time-invariant (eg, sex) and time-varying (eg, environmental exposure) risk factors.To demonstrate the use of latent class growth analysis (LCGA) in defining phenotypes of wheeze and examining the effects of causative factors, using repeated questionnaires in an urban birth cohort study.We gathered repeat questionnaire data on wheeze from 689 children ages 3 through 108 months (n = 7,048 questionnaires) and used LCGA to identify wheeze phenotypes and model the effects of time-invariant (maternal asthma, ethnicity, prenatal environmental tobacco smoke, and child sex) and time-varying (cold/influenza [flu] season) risk factors on prevalence of wheeze in each phenotype.LCGA identified four wheezing phenotypes: never/infrequent (47.1%), early-transient (37.5%), early-persistent (7.6%), and late-onset (7.8%). Compared with children in the never/infrequent phenotype, maternal asthma was a risk factor for the other 3 phenotypes; Dominican versus African American ethnicity was a risk factor for the early-transient phenotype; and male sex was a risk factor for the early-persistent phenotype. The prevalence of wheeze was higher during the cold/flu season than otherwise among children in the early-persistent phenotype (P = .08).This is the first application of LCGA to identify wheeze phenotypes in asthma research. Unlike other methods, this modeling technique can accommodate questionnaire data collected at irregularly spaced age intervals and can simultaneously identify multiple trajectories of health outcomes and associations with time-invariant and time-varying causative factors.

S A T U R D A Y 72 1. Ambient Air Pollution and Allergic Sensitization: Results from the National Health and Examination Survey (NHANES) 20052006 C. Weir, K. Yeatts, W. Vizuete, S. London, P. M. Salo, R. Jaramillo, D. Zeldin; University of North Carolina Chapel Hill, Chapel Hill, NC, National Institute of Environmental Health Sciences, Research Triangle Park, NC, SRA International Inc., Durham, NC, National Institute of Environmental Health Sciences, Durham, NC. RATIONALE: Allergic sensitization is a risk factor for asthma and allergic disease. To date, no large-scale population-based studies have examined the relationship between air pollution and allergic sensitization in the U.S.We hypothesized that exposure to NO2, PM2.5, and O3 would be associated with increased odds of allergic sensitization. METHODS: We analyzed air pollution estimates from monitored data and the Community Multiscale Air Quality Model linked to participants ages 6 and older from NHANES. We assessed sensitization to five categories of allergen-specific IgE: 1) any of 19 allergens; 2) inhalant allergens; 3) outdoor allergens; 4) indoor allergens; and 5) food allergens. Logistic regression was used to produce odds ratios per 10 parts per billion for NO2 and ozone, per 10 mg/m 3 for PM10 and per 1 mg/m 3 for PM2.5 . RESULTS: Monitored and modeled estimates of NO2 were associated with any (n54331 OR51.25, 95% CI 1.10 1.41, n56227 OR51.15, 95% CI 1.05 1.26), inhalant (n54331 OR51.23 95% CI 1.07 1.41, n56227 OR51.17, 95% CI 1.04 1.33), indoor (n54331 OR51.15 95% CI 1.01 -1.30, n56227 OR51.17 95% CI 1.05 1.31) respectively. Monitored NO2 was associated with outdoor allergen-specific IgE (n54331 OR51.25, 95% CI 1.04 1.49). Monitored and modeled PM2.5 was associated with indoor allergen-specific IgE (n55298 OR51.05 95% CI 1.03 -1.08, n56227 OR51.04 95% CI 1.03 1.06). CONCLUSIONS: Exposure to ambient air pollution is associated with allergic sensitization in the U.S. population.

Background Prior research has linked maternal prenatal and postnatal mental health with the subsequent development of asthma in children. However, this relationship has not been examined in inner-city African Americans and Hispanics, populations at high risk for asthma. Objective To determine the relationship of maternal demoralization with wheeze, specific wheeze phenotypes, and seroatopy among children living in a low-income, urban community. Methods African American and Dominican women aged 18 to 35 years residing in New York City (the Bronx and Northern Manhattan) were recruited during pregnancy (n = 279). Maternal demoralization (ie, psychological distress) was measured both prenatally and postnatally by validated questionnaire. Outcomes included wheeze, transient (birth to 2.5 years of age), late onset (3–5 years), and persistent (birth to 5 years of age), evaluated via questionnaire and total and indoor allergen specific IgE (at birth and ages 2, 3, and 5 years). Logistic regression with generalized estimating equations assessed the association of demoralization with wheeze and atopy. Multinomial regression explored associations between demoralization and specific wheeze phenotypes. Results Prenatal demoralization significantly predicted overall wheeze (adjusted odds ratio OR, 1.66; 95% confidence interval [CI], 1.29–2.14), transient wheeze (OR, 2.25; 95% CI, 1.34–3.76), and persistent wheeze (OR, 2.69; 95% CI, 1.52–4.77). No association was found between demoralization and IgE after adjustment (total IgE: OR, 1.04; 95% CI, 0.74–1.45; any specific IgE: OR, 0.96; 95% CI, 0.57–1.60). Conclusions In this inner-city cohort, prenatal demoralization was associated with transient and persistent wheeze. Understanding how maternal demoralization influences children's respiratory health may be important for developing effective interventions among disadvantaged populations.

L8 Prenatal and Postnatal Exposure to Polycyclic Aromatic Hydrocarbons and Asthma: Effect of Atopy at Ages 5-6 yrs in an Urban Birth Cohort K. Jung, S. Hsu, K. Moors, K. Bernabe, B. Yan, S. N. Chillrud, R. Whyatt, M. Perzanowski, L. Hoepner, I. Goldstein, B. Zhang, D. Camann, P. L. Kinney, F. P. Perera, R. L. Miller; Columbia University, New York, NY, Lamont-Doherty Earth Observatory, Palisades, NY, Mailman School of Public Health, New York, NY, Southwest Research Institute, San Antonio, TX, Division of Pulmonary, New York, NY. RATIONALE: Research suggests that exposure to traffic-related air pollutants may induce or trigger asthma. However, the combined effects of prenatal and early postnatal individual exposure to polycyclic aromatic hydrocarbons (PAHs) on respiratory outcomes have not been examined. We hypothesized that exposure to PAHs, and pyrene specifically, would be differentially associated with asthma among atopic and non-atopic children. METHODS: Prenatal PAH exposure was assessed by personal air monitoring over 48-hrs and postnatal PAH exposure by two-week residential indoor monitoring between ages 5/6 in the Columbia Center for Children’s Environmental Health birth cohort. PAH was dichotomized into +8PAHnonvolatile (MW 228-278) and pyrene. High PAH exposure group was defined as high-prenatal (upper 50%) and high-postnatal (upper 50%) exposure and compared to the rest of groups (Low-low, low-high, and high-low). Asthma was defined by validated questionnaires. Children with any indoor allergen specific IgE >_ 0.35 IU/ml were considered atopic. RESULTS: Among non-atopic children (n 5 152), a positive association between high pyrene levels and current asthma (OR 3.01, p5 0.017, 95% CI[1.2-7.5]) and emergency room visits (OR 2.50, p5 0.038, 95%CI[1.055.9]) was obtained in logistic regression analyses. Also among non-atopic children, an inverse association was found between high +8PAHnonvolatile exposure and current asthma (OR 0.31, p 5 0.033, 95%CI[0.11-0.91]) and wheeze (OR 0.24, p5 0.005, 95%CI[0.09-0.67]). Among atopic children (n 5 62), no significant associations were found between pyrene or +8PAHnonvolatile exposure and asthma-related symptoms. CONCLUSIONS: Among non-atopic children, high prenatal and postnatal exposure to pyrene was associated with greater odds of asthma-related symptoms, whereas combined prenatal and postnatal S8PAHnonvolatile exposure was associated with lower odds of asthma-related symptoms.

Chromosomal aberrations (CAs) and translocations (TRNS) (subtype of CAs) are a validated biomarker of increased cancer risk in adults. Prenatal exposure to semi-volatile air PAH predicts levels of stable CAs in neonatal (cord) blood. Urinary levels of 1 and 2 naphthol, metabolites of naphthalene, an IARC class2b possible carcinogen, appear elevated in the CCCEH birth cohort. We hypothesize that concurrent exposure to naphthalene is associated with development of CAs and TRNS in children. Whole blood from 113 five year old children (68 girls) participating in the CCCEH birth cohort composed of Dominican (DomAm) (N=66) and African-Americans (AfrAm) (N=47) was processed fresh for Whole Chromosome Paint (WCP)-Fluorescent In Situ Hybridization using WCP for chromosomes 1-6. 400 Cell Equivalents [CE]) were scored for each child. TRNS were scored in accordance with the PAINT convention and frequencies were expressed per 100 CE. Levels of PAH metabolites were measured using MSGC in spot urine samples (Sjodin laboratory, CDC) collected concurrently and adjusted for urine specific gravity (SG). We examined predictors of presence of CA's or TRNS. For predicting frequency of CA and TRNS, mean ratios were derived for doubling of naphthol levels using negative binomial models. Results: 35 children had CA's and 20 had TRNS. Geometric means among AfrAm were 3490.2 for 1naphthol, and 3005.1 for 2naphthol, and 3336.4 and 5256.6 for 1 & 2naphthol in DomAm children. Levels of 1& 2 napthol did not vary with presence of a smoker in the child's home. 2naphthol (but not 1napthol) was higher in girls (p= 0.08) and in DomAm (p=0.01). After adjusting for gender and ethnicity, presence of both CA's and TRNS was predicted by increasing levels of 1- and 2- naphthol: OR for presence of CA's with increasing 1naphthol: (1.23; 95%CI:1.01, 1.48); and with 2napthol (1.19; 0.90, 1.56), but the effect was significantly higher in DomAms for both 1naphthol (1.63;1.21, 2.19) & 2naphthol (1.44; 1.02, 2.04). For TRNS, the OR was 1.55 (1.11,2.17) for 1naphthol, and 1.92 (1.20-3.08) for 2naphthol. Frequency of CA's was predicted by 1naph (MR1.38; 1.10, 1.72) in DomAm but not in AfrAm (RR0.90; 0.65, 1.25). The association between naphthols and frequency of TRNS did not differ by ethnicity. To examine possible dose-response, levels of 2naphthol were grouped into tertiles using the lowest tertile as the referent group. After adjusting for gender/ethnicity, the proportion with TRNS present increased with increasing 2naphthol (though trend p = 0.09). Children with 2napthol in the highest tertile were significantly more likely to have translocations (OR 4.29; 95% CI: 1.11-16.55) when compared with children in the lowest tertile. Similarly, children with increasing 2-naphthol levels had increasing frequency of TRNS though the overall trend was not significant: mean TRNS frequencies for children in the highest tertile of exposure had a ratio of 3.23; (95%CI: 0.85-12.50) compared with those in the lowest tertile. The effect of increasing naphthol on aberrations or translocations was not dominated by any one chromosome, in contrast to our findings in newborns and prenatal air-PAH. Together these findings support our earlier findings that PAH exposure is associated with formation of TRNS, and suggests a dose response pattern with exposure to naphthalene, and an ethnic difference in susceptibility to formation of CAs. Citation Information: Cancer Prev Res 2010;3(12 Suppl):B32.

Chromosomal aberrations (CAs) measured in cord blood are associated with maternal exposure to air Polycyclic Aromatic Hydrocarbons (PAH) in newborns from the Columbia Center for Children's Environmental Health (CCCEH). We hypothesize that naphthalene, a PAH not measureable in air levels and an IARC classified potential carcinogen, might be associated with chromosomal aberrations. Now in 90 five yr olds from this cohort we examined the association between stable CAs (including translocations) scored using whole chromosome painting Fluorescent In Situ Hybridization in chromosomes 1-6, 11,12,14,19 in peripheral blood, and specific gravity adjusted 1OH and 2OH naphthalene (1OHnaph and 2OHnaph) metabolites measured in simultaneously collected urine, using an automated liquid-liquid extraction and quantified by gas chromatography/isotope dilution high-resolution mass spectrometry. Dominican American (DA) 5 yr olds (n=50) had higher specific 2OHnaph levels (mean: 12535.9 ng/m3; SD: 22227.6) than African American (AA) 5 yr olds (n=40)(mean: 4239.2 SD: 3397.0),(Wilcoxon test, p=0.02) consistent with differences previously seen in the entire CCCEH cohort. Bivariate correlations between frequencies of CAs and 1OHnaph and 2OHnaph stratified by sex or ethnic group suggested an ethnic disparity in the association between CAs and naphthalenes. Negative binomial models were used to examine whether this association was dependent on ethnicity, controlling for sex. 1OHnaph increased total stable CAs frequency in chromosomes 1-6 (r=0.24, p= 0.03), though this increase was only in DA (r=0.47, p=0.0006), not AA (r=0.09). Controlling for sex, the ethnic disparity in the association differs significantly (p=0.006). Frequency of translocations (a subgroup of stable CAs) also increased with increasing levels of 1OHNaph (r=0.20;p=0.07), particularly in DA(r=0.36; p=0.01), not in AA (r=0.07; p=0.0.6);controlling for sex, the ethnic disparity in association was significant (p Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-402.

In a longitudinal cohort of approximately 700 children in New York City, the prevalence of asthma (>25%) is among the highest in the US. This high risk may in part be caused by transplacental exposure to traffic-related polycyclic aromatic hydrocarbons (PAHs) but biomarkers informative of PAH-asthma relationships is lacking. We here hypothesized that epigenetic marks associated with transplacental PAH exposure and/or childhood asthma risk could be identified in fetal tissues. Mothers completed personal prenatal air monitoring for PAH exposure determination. Methylation sensitive restriction fingerprinting was used to analyze umbilical cord white blood cell (UCWBC) DNA of 20 cohort children. Over 30 DNA sequences were identified whose methylation status was dependent on the level of maternal PAH exposure. Six sequences were found to be homologous to known genes having one or more 5'-CpG island(s) (5'-CGI). Of these, acyl-CoA synthetase long-chain family member 3 (ACSL3) exhibited the highest concordance between the extent of methylation of its 5'-CGI in UCWBCs and the level of gene expression in matched fetal placental tissues in the initial 20 cohort children. ACSL3 was therefore chosen for further investigation in a larger sample of 56 cohort children. Methylation of the ACSL3 5'-CGI was found to be significantly associated with maternal airborne PAH exposure exceeding 2.41 ng/m(3) (OR = 13.8; p

The frequency of right-to-left shunt through a patent foramen ovale is increased in hemodynamically stable patients without preexisting cardiopulmonary disease with acute pulmonary embolism. This is associated with a greater degree of perfusion abnormalities as quantified by perfusion scan and the presence of tricuspid regurgitation.

Rationale Studies have reported a protective effect of early life exposure to endotoxin against the development of allergic diseases, but few have examined an inner-city population. Due to temporal differences between increased hygienic living in NYC (early 20th century) and the asthma increase (later 20th century), we hypothesized that endotoxin's protective effect would not be observed in this inner-city community. Methods As part of an ongoing prospective birth cohort study sponsored by CCCEH, children of Dominican and African-American mothers living in NYC underwent detailed questionnaires quarterly, home dust collection, and IgE measurement. The 176 dust samples collected thus far from bedroom floors at age 12 months were extracted in pyrogen-free water with tween and assayed for endotoxin by LAL assay. Results The geometric mean of endotoxin in the dust was 78 EU/mg [95% CI 65-93]. Endotoxin concentrations were slightly higher in homes of mothers reporting weekly cockroach sightings (88 EU/mg vs. 72 EU/mg, p=0.3) or pet ownership (93 EU/mg vs. 75 EU/mg, p=0.4), and significantly higher with weekly mouse sightings (108 EU/mg vs. 69 EU/mg, p=0.043). There was no association between those children living in homes with endotoxin concentrations in the highest quartile (>163 EU/mg) and wheeze at 12 (RR 0.92 [0.8-1.1]) or 24 months (RR 0.96 [0.8-1.1]); doctor diagnosed eczema at 12 (RR 0.94 [0.8-1.1]) or 24 months (RR 1.0 [0.8-1.3]); or total IgE in the highest quartile at 24 months (RR 1.1 [0.8-1.5]). Conclusions At this age in this inner-city community we observed no association between high endotoxin and a lower prevalence of early markers of allergic disease, while endotoxin concentrations were comparable to those reported elsewhere.

Rationale Influenza vaccination is recommended for women who are pregnant during the influenza season. Nonetheless, the development of B cell priming to influenza antigens in utero is controversial. We hypothesized that neonatal B cells will exhibit antigen specific immune responses following influenza vaccination of the pregnant mother. Methods Thirty pregnant women were recruited and vaccinated (mean gestation 25.80 ± 0.82 weeks) during the influenza season. Fluzone and Matrix Protein (MP)-antigen specific IgM and IgG titers were measured by ELISA in mothers pre- and postpartum and newborns postpartum. Results 18/30 (60%) mothers showed a positive Fluzone antigens-IgM response (mean Optical Density (OD) ratio 5.57 ± SE 1.11)[Positive response defined as OD post vaccine/OD pre vaccine >2]. 14/30 (46.7%) had a positive response to MP antigens (mean OD ratio 6.93 ± 2.25). In comparison, 9/17 (53%) newborns demonstrated a Fluzone-specific IgM response [OD 2 fold >OD measured in the cohort born to nonvaccinated mothers]. Their mean Fluzone IgM averaged 0.041 ± 0.013 ( p p p Conclusions The increased Fluzone, MP-specific IgM levels suggest that in utero B cell priming to influenza antigens occurs following vaccination of the mother during pregnancy.

Background Anaphylaxis is a severe, life-threatening allergic reaction that affects both children and adults in the United States. However, data regarding the incidence and prevalence of anaphylaxis and the number of deaths caused by it are limited. Objective To provide a better understanding of the magnitude of the problem of anaphylaxis in the United States. Methods A thorough review of the current medical literature was conducted to obtain prevalence estimates on each of the 4 major subtypes of anaphylaxis (food, drugs, latex, and insect stings). We calculated an overall estimate of the risk of anaphylaxis by using only estimates that are specifically derived from epidemiologic studies measuring anaphylaxis in the general population. Results Known rates or cases of anaphylaxis were 0.0004% for food, 0.7% to 10% for penicillin, 0.22% to 1% for radiocontrast media, and 0.5% to 5% after insect stings. There were 220 cases after latex exposure. Considering the 1999 US population of 272 million, the population at risk for anaphylaxis from food is 1099, from penicillin is 1.9 million to 27.2 million, from radiocontrast media is 22 000 to 100 000, from latex is 220, and from insect stings is 1.36 million to 13.6 million. These calculations yield a total of 3.29 million to 40.9 million individuals at risk of anaphylaxis. Conclusion The occurrence of anaphylaxis in the US is not as rare as is generally believed. On the basis of our figures, the problem of anaphylaxis may, in fact, affect 1.21% to 15.04% of the US population.