Manuel Villareal

A Comparison of Proximity and Land Use Regression Traffic Exposure Models and Wheezing in Infants

Background We previously reported an association between infant wheezing and residence < 100 m from stop-and-go bus and truck traffic. The use of a proximity model, however, may lead to exposure misclassification. Objective Results obtained from a land use regression (LUR) model of exposure to truck and bus traffic are compared with those obtained with a proximity model. The estimates derived from the LUR model were then related to infant wheezing. Methods We derived a marker of diesel combustion—elemental carbon attributable to traffic sources (ECAT)—from ambient monitoring results of particulate matter with aerodynamic diameter < 2.5 μm. We developed a multiple regression model with ECAT as the outcome variable. Variables included in the model were locations of major roads, bus routes, truck traffic count, and elevation. Model parameter estimates were applied to estimate individual ECAT levels at infants’ homes. Results The levels of estimated ECAT at the monitoring stations ranged from 0.20 to 1.02 μg/m3. A LUR model of exposure with a coefficient of determination (R2) of 0.75 was applied to infants’ homes. The mean (± SD) ambient exposure of ECAT for infants previously categorized as unexposed, exposed to stop-and-go traffic, or exposed to moving traffic was 0.32 ± 0.06, 0.42 ± 0.14, and 0.49 ± 0.14 μg/m3, respectively. Levels of ECAT from 0.30 to 0.90 μg/m3 were significantly associated with infant wheezing. Conclusions The LUR model resulted in a range of ECAT individually derived for all infants’ homes that may reduce the exposure misclassification that can arise from a proximity model.

High environmental relative moldiness index during infancy as a predictor of asthma at 7 years of age

BACKGROUND Mold exposures may contribute to the development of asthma, but previous studies have lacked a standardized approach to quantifying exposures. OBJECTIVE To determine whether mold exposures at the ages of 1 and/or 7 years were associated with asthma at the age of 7 years. METHODS This study followed up a high-risk birth cohort from infancy to 7 years of age. Mold was assessed by a DNA-based analysis for the 36 molds that make up the Environmental Relative Moldiness Index (ERMI) at the ages of 1 and 7 years. At the age of 7 years, children were evaluated for allergic sensitization and asthma based on symptom history, spirometry, exhaled nitric oxide, and airway reversibility. A questionnaire was administered to the parent regarding the childs asthma symptoms and other potential cofactors. RESULTS At the age of 7 years, 31 of 176 children (18%) were found to be asthmatic. Children living in a high ERMI value (≥5.2) home at 1 year of age had more than twice the risk of developing asthma than those in low ERMI value homes (<5.2) (adjusted odds ratio [aOR], 2.6; 95% confidence interval [CI], 1.10-6.26). Of the other covariates, only parental asthma (aOR, 4.0; 95% CI, 1.69-9.62) and allergic sensitization to house dust mite (aOR, 4.1; 95% CI, 1.55-11.07) were risk factors for asthma development. In contrast, air-conditioning at home reduced the risk of asthma development (aOR, 0.3; 95% CI, 0.14-0.83). A high ERMI value at 7 years of age was not associated with asthma at 7 years of age. CONCLUSIONS Early exposure to molds as measured by ERMI at 1 year of age, but not 7 years of age, significantly increased the risk for asthma at 7 years of age.

House dust (1-3)-β-D-glucan and wheezing in infants

Background:  (1–3)‐β‐d‐glucan is a fungal cell wall component, suspected to cause respiratory symptoms in adults. However, very little is known on the possible health effects of (1–3)‐β‐d‐glucan during infancy. We examined the association between (1–3)‐β‐d‐glucan exposure and the prevalence of allergen sensitization and wheezing during the first year of life in a birth cohort of 574 infants born to atopic parents. Endotoxin exposure was included as a possible confounder.

Exposure to Traffic-related Particles and Endotoxin during Infancy Is Associated with Wheezing at Age 3 Years

RATIONALE Murine models demonstrate a synergistic production of reactive oxygen species on coexposure to diesel exhaust particles and endotoxin. OBJECTIVES It was hypothesized that coexposure to traffic-related particles and endotoxin would have an additive effect on persistent wheezing during early childhood. METHODS Persistent wheezing at age 36 months was assessed in the Cincinnati Childhood Allergy and Air Pollution Study, a high-risk birth cohort. A time-weighted average exposure to traffic-related particles was determined by applying a land-use regression model to the homes, day cares, and other locations where children spent time from birth through age 36 months. Indoor levels of endotoxin were measured from dust samples collected before age 12 months. The relationship between dichotomized (or=75th percentile) traffic-related particle and endotoxin exposure and persistent wheezing, controlling for potential covariates, was examined. MEASUREMENTS AND MAIN RESULTS Persistent wheezing at age 36 months was significantly associated with exposure to increased levels of traffic-related particles before age 12 months (OR = 1.75; 95% confidence interval, 1.07-2.87). Coexposure to endotoxin had a synergistic effect with traffic exposure on persistent wheeze (OR = 5.85; 95% confidence interval, 1.89-18.13) after adjustment for significant covariates. CONCLUSIONS The association between traffic-related particle exposure and persistent wheezing at age 36 months is modified by exposure to endotoxin. This finding supports prior toxicological studies demonstrating a synergistic production of reactive oxygen species after coexposure to diesel exhaust particles and endotoxin. The effect of early versus later exposure to traffic-related particles, however, remains to be studied because of the high correlation between exposure throughout the first 3 years of life.

Environmental risk factors of rhinitis in early infancy

Previous studies of allergic rhinitis in children have not documented the environmental risk factors for infants at age one. We examined the relationship of environmental tobacco smoke (ETS) and visible mold exposures on the development of allergic rhinitis, rhinitis and upper respiratory infection (URI) in a birth cohort where at least one parent was skin prick test (SPT) positive. ETS exposure and upper respiratory symptoms were obtained by questionnaires. Visible mold was classified as none, low or high during home visit. Infants had a SPT at age one. After adjustment for potential confounders, exposure to >20 cigarettes per day was associated with an increased risk of developing allergic rhinitis at age one [odds ratio (OR) = 2.7; 95% CI 1.04–6.8] and rhinitis symptoms during the first year (OR = 1.9; 95% CI 1.1–3.2). Infants with low (OR = 1.5; 95% CI 1.1–2.3) or high (OR = 5.1; 95% CI 2.2–12.1) levels of visible mold in their homes were more likely to have more frequent URI during the first year. Older siblings were protective for development of both rhinitis symptoms and allergic rhinitis. This study suggests that ETS exposure, rather than visible mold, is associated with rhinitis and allergic rhinitis in infants. The analysis also suggests that mold may be a stronger risk factor for URI that ETS.

Mold exposure during infancy as a predictor of potential asthma development

BACKGROUND Exposure to mold has been associated with exacerbation of asthma symptoms in children. OBJECTIVE To report how the presence of visible mold and exposure to (1-3)-beta-D-glucan in infancy affects the risk of asthma at the age of 3 years as defined by an Asthma Predictive Index (API). METHODS Visible mold was evaluated by means of home inspection. (1-3)-beta-D-glucan levels were measured in settled dust. Children were considered to be at high risk for asthma at later ages if they reported recurrent wheezing at the age of 3 years and met at least 1 of 3 major or 2 of 3 minor API criteria. RESULTS Children aged 3 years with high visible mold in the home during infancy were 7 times more likely to have a positive API than were those with no visible mold (adjusted odds ratio [aOR], 7.1; 95% confidence interval [CI], 2.2-12.6). In contrast, at low (1-3)-beta-D-glucan levels (< 22 microg/g), children were at increased risk of a positive API (aOR, 3.4; 95% CI, 0.5-23.5), whereas those with high (1-3)-beta-D-glucan levels (> 133 microg/g) were at decreased risk (aOR, 0.6; 95% CI, 0.2-1.6). Of the other covariates, mothers smoking was the strongest significant risk factor for the future development of asthma based on a positive API (aOR, 4.4; 95% CI, 1.7-11.6). CONCLUSIONS The presence of high visible mold and mothers smoking during infancy were the strongest risk factors for a positive API at the age of 3 years, suggesting an increased risk of asthma. High (1-3)-beta-D-glucan exposure seems to have an opposite effect on API than does visible mold.

Traffic-Related Air Pollution Exposure in the First Year of Life and Behavioral Scores at 7 Years of Age

Background: There is increasing concern about the potential effects of traffic-related air pollution (TRAP) on the developing brain. The impact of TRAP exposure on childhood behavior is not fully understood because of limited epidemiologic studies. Objective: We explored the association between early-life exposure to TRAP using a surrogate, elemental carbon attributed to traffic (ECAT), and attention deficit/hyperactivity disorder (ADHD) symptoms at 7 years of age. Methods: From the Cincinnati Childhood Allergy and Air Pollution Study (CCAAPS) birth cohort we collected data on exposure to ECAT during infancy and behavioral scores at 7 years of age. Children enrolled in CCAAPS had at least one atopic parent and a birth residence either < 400 m or > 1,500 m from a major highway. Children were followed from infancy through 7 years of age. ECAT exposure during the first year of life was estimated based on measurements from 27 air sampling sites and land use regression modeling. Parents completed the Behavioral Assessment System for Children, 2nd Edition, when the child was 7 years of age. ADHD-related symptoms were assessed using the Hyperactivity, Attention Problems, Aggression, Conduct Problems, and Atypicality subscales. Results: Exposure to the highest tertile of ECAT during the child’s first year of life was significantly associated with Hyperactivity T-scores in the “at risk” range at 7 years of age, after adjustment [adjusted odds ratio (aOR) = 1.7; 95% CI: 1.0, 2.7]. Stratification by maternal education revealed a stronger association in children whose mothers had higher education (aOR = 2.3; 95% CI: 1.3, 4.1). Conclusions: ECAT exposure during infancy was associated with higher Hyperactivity scores in children; this association was limited to children whose mothers had more than a high school education.

Relative moldiness index as predictor of childhood respiratory illness.

The results of a traditional visual mold inspection were compared to a mold evaluation based on the Relative Moldiness Index (RMI). The RMI is calculated from mold-specific quantitative PCR (MSQPCR) measurements of the concentration of 36 species of molds in floor dust samples. These two prospective mold evaluations were used to classify the mold condition in 271 homes of infants. Later, the development of respiratory illness was measured in the infants living in these homes and the predictive value of each classification system was evaluated.The binary classification of homes as either moldy or non-moldy by on-site visual home inspection was not predictive of the development of respiratory illness (wheeze and/or rhinitis) (P=0.27). Conversely, a method developed and validated in this paper, using the RMI index fit to a logistic function, can be used to predict the occurrence of illness in homes and allows stake-holders the choice among various levels of risk.

Associations between Multiple Environmental Exposures and Glutathione S-transferase P1 on Persistent Wheezing in a Birth Cohort

OBJECTIVE To determine the impact of environmental exposures (diesel exhaust particle [DEP], environmental tobacco smoke [ETS], and mold) that may contribute to oxidative stress on persistent wheezing in the Cincinnati Childhood Allergy and Air Pollution Study (CCAAPS) birth cohort and to determine how the impact of these exposures is modified by the GST-P1 Ile105Val polymorphism. STUDY DESIGN A land-use regression model was used to derive an estimate of each childs DEP exposure. ETS exposure was determined by questionnaire data. Each childs home was evaluated for visible mold by a trained professional. Children in the CCAAPS cohort were genotyped for the GST-P1 polymorphism (n = 570). Persistent wheezing was defined as wheezing at both 12 and 24 months. RESULTS High DEP exposure conferred increased risk for wheezing phenotypes but only among the Val(105) allele carriers. Infants with multiple exposures were significantly more likely to persistently wheeze despite their genotype. CONCLUSION There is evidence for an environmental effect of DEP among carriers of the GST-P1 Val(105) allele in the development of persistent wheezing in children. The protective effect of the GST-P1 Ile(105) genotype may be overwhelmed by multiple environmental exposures that converge on oxidative stress pathways.

Breast-feeding, aeroallergen sensitization, and environmental exposures during infancy are determinants of childhood allergic rhinitis

BACKGROUND Infant predictors of early childhood allergic rhinitis (AR) are poorly understood. OBJECTIVE We sought to identify environmental exposures and host factors during infancy that predict AR at age 3 years. METHODS High-risk children from greater Cincinnati were followed annually from ages 1 to 3 years. AR was defined as sneezing, runny, or blocked nose in the prior 12 months and a positive skin prick test (SPT) response to 1 or more aeroallergens. Environmental and standardized medical questionnaires determined exposures and clinical outcomes. Primary activity area dust samples were analyzed for house dust endotoxin (HDE) and (1-3)-beta-D-glucan. Fine particulate matter sampled at 27 monitoring stations was used to estimate personal elemental carbon attributable to traffic exposure by using a land-use regression model. RESULTS Of 361 children in this analysis, 116 had AR, and 245 were nonatopic and nonsymptomatic. Prolonged breast-feeding in African American children (adjusted odds ratio [aOR], 0.8; 95% CI, 0.6-0.9) and multiple children in the home during infancy was protective against AR (aOR, 0.4; 95% CI, 0.2-0.8). Food SPT response positivity and tree SPT response positivity in infancy increased the risk of AR at age 3 years (aOR of 4.4 [95% CI, 2.1-9.2] and aOR of 6.8 [95% CI, 2.5-18.7], respectively). HDE exposure was associated with AR; the effect was dependent on exposure level. Elemental carbon attributable to traffic and environmental tobacco smoke exposure showed no effect on AR. CONCLUSION Prolonged breast-feeding in African American subjects and multiple children in the home during infancy reduced the risk of AR at age 3 years. SPT response positivity to food and tree allergens enhanced risk. The HDE effect on AR was related to exposure.