Maria José Rosa

Children’s Urinary Phthalate Metabolites and Fractional Exhaled Nitric Oxide in an Urban Cohort

RATIONALE Phthalates are used widely in consumer products. Exposure to several phthalates has been associated with respiratory symptoms and decreased lung function. Associations between childrens phthalate exposures and fractional exhaled nitric oxide (Fe(NO)), a biomarker of airway inflammation, have not been examined. OBJECTIVES We hypothesized that urinary concentrations of four phthalate metabolites would be positively associated with Fe(NO) and that these associations would be stronger among children with seroatopy or wheeze. METHODS In an urban ongoing birth cohort, 244 children had phthalate metabolites determined in urine collected on the same day as Fe(NO) measurement. Repeated sampling gathered 313 observations between ages 4.9 and 9.1 years. Seroatopy was assessed by specific IgE. Wheeze in the past year was assessed by validated questionnaire. Regression models used generalized estimating equations. MEASUREMENTS AND MAIN RESULTS Log-unit increases in urinary concentrations of metabolites of diethyl phthalate (DEP) and butylbenzyl phthalate (BBzP) were associated with a 6.6% (95% confidence interval [CI] 0.5-13.1%) and 8.7% (95% CI, 1.9-16.0%) increase in Fe(NO), respectively, adjusting for other phthalate metabolites and potential covariates/confounders. There was no association between concentrations of metabolites of di(2-ethylhexyl) phthalate or di-n-butyl phthalate and Fe(NO). There was no significant interaction by seroatopy. The BBzP metabolite association was significantly stronger among children who wheeze (P = 0.016). CONCLUSIONS Independent associations between exposures to DEP and BBzP and Fe(NO) in a cohort of inner-city children were observed. These results suggest that these two ubiquitous phthalates, previously shown to have substantial contributions from inhalation, are positively associated with airway inflammation in children.

Exhaled NO Among Inner-city Children in New York City

Background. Fractional exhaled nitric oxide (FeNO) has been proposed as a biomarker of airway inflammation for cohort studies of asthma. Objectives. To assess the association between FeNO and asthma symptoms among 7-year-old children living in an inner-city community. To test the association between environmental tobacco smoke (ETS) exposure (previous and current) and FeNO among these children. Methods. As part of a longitudinal study of asthma, children recruited in Head Start centers at age 4 had offline FeNO and lung function testing at age 7. Children with allergen-specific immunoglobulin E (IgE) (≥0.35 IU/mL) at age 7 were considered seroatopic. ETS exposure at ages 4 and 7 was assessed by questionnaire. Results. Of 144 participating children, 89 had complete questionnaire data and achieved valid FeNO and lung function tests. Children with reported wheeze in the previous 12 months (n = 19) had higher FeNO than those without wheeze (n = 70) (geometric means 17.0 vs. 11.0 ppb, p = .005). FeNO remained significantly associated with wheeze (p = .031), after adjusting for seroatopy and forced expiratory volume in 1 second (FEV1) in multivariable regression. FeNO at age 7 was positively associated with domestic ETS exposure at age 4 (29%) (β = 0.36, p = .015) but inversely associated with ETS exposure at age 7 (16%) (β = −0.74, p < .001). Conclusions. Given its association with current wheeze, independent of seroatopy and lung function, FeNO provides a relevant outcome measure for studies in inner-city communities. While compelling, the positive association between ETS exposure at age 4 and a marker of airway inflammation at age 7 should be confirmed in a larger study.

Prenatal Nitrate Exposure and Childhood Asthma. Influence of Maternal Prenatal Stress and Fetal Sex

Rationale: Impact of ambient pollution upon childrens asthma may differ by sex, and exposure dose and timing. Psychosocial stress can also modify pollutant effects. These associations have not been examined for in utero ambient nitrate exposure. Objectives: We implemented Bayesian‐distributed lag interaction models to identify sensitive prenatal windows for the influence of nitrate (NO3−) on child asthma, accounting for effect modification by sex and stress. Methods: Analyses included 752 mother‐child dyads. Daily ambient NO3− exposure during pregnancy was derived using a hybrid chemical transport (Geos‐Chem)/land‐use regression model and natural log transformed. Prenatal maternal stress was indexed by a negative life events score (high [>2] vs. low [≤2]). The outcome was clinician‐diagnosed asthma by age 6 years. Measurements and Main Results: Most mothers were Hispanic (54%) or black (29%), had a high school education or less (66%), never smoked (80%), and reported low prenatal stress (58%); 15% of children developed asthma. BDILMs adjusted for maternal age, race, education, prepregnancy obesity, atopy, and smoking status identified two sensitive windows (7‐19 and 33‐40 wk gestation), during which increased NO3− was associated with greater odds of asthma, specifically among boys born to mothers reporting high prenatal stress. Cumulative effects of NO3− across pregnancy were also significant in this subgroup (odds ratio = 2.64, 95% confidence interval = 1.27‐5.39; per interquartile range increase in ln NO3−). Conclusions: Prenatal NO3− exposure during distinct sensitive windows was associated with incident asthma in boys concurrently exposed to high prenatal stress.

Domestic airborne black carbon levels and 8-isoprostane in exhaled breath condensate among children in New York City

BACKGROUND Exposure to airborne black carbon (BC) has been associated with asthma development, respiratory symptoms and decrements in lung function. However, the mechanism through which BC may lead to respiratory symptoms has not been completely elucidated. Oxidative stress has been suggested as a potential mechanism through which BC might lead to adverse health outcomes. Exhaled breath condensate (EBC) allows for the non-invasive collection of airway lining fluid containing biomarkers of oxidative stress like 8-isoprostane, a stable by-product of lipid peroxidation. Therefore, we sought to characterize the association between domestic airborne BC concentrations and 8-isoprostane in EBC. MATERIALS AND METHODS Seven- and eight-year-old children participated in an asthma case-control study in New York City. During home visits, air samples and EBC were collected. Seven day averages of domestic levels of particulate matter <2.5μm (PM2.5), BC and environmental tobacco smoke (ETS) were measured. Urea and 8-isoprostane were measured by liquid chromatography tandem mass spectrometry (LC/MS/MS) in EBC. RESULTS In univariate models, PM2.5 and BC, but not ETS, were significantly associated with increases in 8-isoprostane in the EBC (β=0.006 and β=0.106 respectively, p<0.05 for both). These associations remained statistically significant for both PM2.5 and BC after adjustment for covariates. In a co-pollutant model including PM2.5, BC and ETS, only BC remained a statistically significant predictor of 8-isoprostane (p<0.05). CONCLUSIONS Our findings suggest the BC fraction of PM might contain exposure relevant to increased oxidative stress in the airways.

Fractional exhaled nitric oxide exchange parameters among 9-year-old inner-city children.

To determine the feasibility of using a multiple flow offline fractional exhaled nitric oxide (FeNO) collection method in an inner‐city cohort and determine this populations alveolar and conducting airway contributions of NO. We hypothesized that the flow independent NO parameters would be associated differentially with wheeze and seroatopy.

Prenatal fine particulate exposure and early childhood asthma: Effect of maternal stress and fetal sex

Background The impact of prenatal ambient air pollution on child asthma may be modified by maternal stress, child sex, and exposure dose and timing. Objective We prospectively examined associations between coexposure to prenatal particulate matter with an aerodynamic diameter of less than 2.5 microns (PM2.5) and maternal stress and childhood asthma (n = 736). Methods Daily PM2.5 exposure during pregnancy was estimated using a validated satellite‐based spatiotemporally resolved prediction model. Prenatal maternal negative life events (NLEs) were dichotomized around the median (high: NLE ≥ 3; low: NLE < 3). We used Bayesian distributed lag interaction models to identify sensitive windows for prenatal PM2.5 exposure on childrens asthma by age 6 years, and determine effect modification by maternal stress and child sex. Results Bayesian distributed lag interaction models identified a critical window of exposure (19‐23 weeks’ gestation, cumulative odds ratio, 1.15; 95% CI, 1.03‐1.26; per interquartile range [1.7 &mgr;g/m3] increase in prenatal PM2.5 level) during which children concomitantly exposed to prenatal PM2.5 and maternal stress had increased risk of asthma. No significant association was seen in children born to women reporting low prenatal stress. When examining modifying effects of prenatal stress and fetal sex, we found that boys born to mothers with higher prenatal stress were most vulnerable (19‐21 weeks’ gestation; cumulative odds ratio, 1.28; 95% CI, 1.15‐1.41; per interquartile range increase in PM2.5). Conclusions Prenatal PM2.5 exposure during sensitive windows is associated with increased risk of child asthma, especially in boys concurrently exposed to elevated maternal stress.

Association of recent exposure to ambient metals on fractional exhaled nitric oxide in 9-11 year old inner-city children

Exposure to ambient metals in urban environments has been associated with wheeze, and emergency room visits and hospitalizations due to respiratory illness. However, the effect of ambient metals exposure on airway inflammation, and how these associations may be modified by seroatopy, has not been determined. Fractional exhaled nitric oxide (FENO) is a reliable proxy marker of airway inflammation. We hypothesized that recent ambient concentrations of Ni, V, Zn and Fe would be associated differentially with proximal and distal fractions of exhaled NO, and that these associations would be modified by seroatopy. As part of the Columbia Center for Childrens Environmental Health (CCCEH) birth cohort study, 9-11 year old children (n=192) were evaluated. Ambient measures of Ni, V, Zn and Fe were obtained from a local central monitoring site and averaged over 9 days based on three 24h measures every third day. Fractional exhaled nitric oxide (FENO) samples were obtained at constant flows of 50 (FENO50), 83 and 100mL/s, and used to determine surrogate measures for proximal (JNO) and alveolar (Calv) inflammation. Seroatopy was determined by specific IgE at age 7. Data were analyzed using multivariable linear regression. Ambient V and Fe concentrations were associated positively with FENO50 (p=0.018, p=0.027). Ambient Fe was associated positively with JNO (p=0.017). Ambient Ni and V concentrations were associated positively with Calv (p=0.004, p=0.018, respectively). A stronger association of Ni concentrations with Calv was observed among the children with seroatopy. These results suggest that ambient metals are associated differentially with different fractions of FENO production, and this relationship may be modified by seroatopy.

Subconstructs of the Edinburgh Postpartum Depression Scale in a postpartum sample in Mexico City

BACKGROUND Postpartum depression is an important cause of morbidity in mothers and children. The Edinburgh Postpartum Depression Scale (EPDS), the most widely used self-reported measure of postpartum depression, was conceived as a one-dimensional measure. However, evidence that depressive symptoms may be experienced differentially across cultural and racial groups highlights the need to examine structural equivalence using factor analysis across populations. Variation in factor structure for the EPDS remains understudied in middle/low income countries. METHODS We examined the factor structure of the EPDS assessed 6 months postpartum in 628 Mexican women in a longitudinal Mexico City birth cohort. We performed exploratory factor analysis (EFA) to determine the optimal fit in our sample and confirmatory factor analysis (CFA) to examine the fit of two- and three-factor models previously reported in Hispanic populations. RESULTS The majority of participants had no more than high school education (77%), maternal age was 28 ± 5.4 years and the mean total EPDS score was 6.72 ± 5.8. Using EFA, we identified that the three-factor model provided the optimal fit, with subscales for depression, anxiety, and anhedonia. CFA confirmed that the three-factor model provided the best fit. LIMITATIONS The study population was lower SES, potentially limiting generalizability. The single administration of the EPDS measure in the postpartum period limited our ability to assess stability over time. CONCLUSIONS Better delineation of the multi-factorial structure of the EPDS will allow a more comprehensive understanding of psychological functioning in postpartum women and better inform diagnosis, management and policy.

Prenatal nitrate air pollution exposure and reduced child lung function: Timing and fetal sex effects

Background: Prenatal particulate air pollution exposure may alter lung growth and development in utero in a time‐sensitive and sex‐specific manner, resulting in reduced lung function in childhood. Such relationships have not been examined for nitrate (NO3‐). Methods: We implemented Bayesian distributed lag interaction models (BDLIMs) to identify sensitive prenatal windows for the influence of NO3‐ on lung function at age 7 years, assessing effect modification by fetal sex. Analyses included 191 mother‐child dyads. Daily ambient NO3‐ exposure over pregnancy was estimated using a hybrid chemical transport (Geos‐Chem)/land‐use regression model. Spirometry was performed at mean (SD) age of 6.99 (0.89) years, with forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) z‐scores accounting for child age, sex, height and race/ethnicity. Results: Most mothers were Hispanic (65%) or Black (22%), had ≤ high school education (67%), and never smoked (71%); 17% children had asthma. BDILMs adjusted for maternal age and education and childs asthma identified an early sensitive window of 6–12 weeks gestation, during which increased NO3‐ was significantly associated with reduced FEV1 z‐scores specifically among boys. BDLIM analyses demonstrated similar sex‐specific patterns for FVC. Conclusion: Early gestational NO3‐ exposure is associated with reduced child lung function, especially in boys. HighlightsPrenatal nitrate exposure is associated with reduced lung function at age 7 yearsLink between prenatal nitrate exposure and lung function deficits is male‐specificSignificant effects occur during early sensitive window of 6‐12 weeks gestation