Cincinnati Childhood Allergy And Air Pollution Study Research Articles

Epigenome-wide association study of fluoride exposure during early adolescence and DNA methylation among U.S. children

Exposure to fluoride in early childhood has been associated with altered cognition, intelligence, attention, and neurobehavior. Fluoride-related neurodevelopment effects have been shown to vary by sex and very little is known about the mechanistic processes involved. There is limited research on how fluoride exposure impacts the epigenome, potentially leading to changes in DNA methylation of specific genes regulating key developmental processes. In the Cincinnati Childhood Allergy and Air Pollution Study (CCAAPS), urine samples were analyzed using a microdiffusion method to determine childhood urinary fluoride adjusted for specific gravity (CUFsg) concentrations. Whole blood DNA methylation was assessed using the Infinium MethylationEPIC BeadChip 850 k Array. In a cross-sectional analysis, we interrogated epigenome-wide DNA methylation at 775,141 CpG loci across the methylome in relation to CUFsg concentrations in 272 early adolescents at age 12 years. Among all participants, higher concentrations of CUF were associated with differential methylation of one CpG (p < 6 × 10−8) located in the gene body of GBF1 (cg25435255). Among females, higher concentrations of CUFsg were associated with differential methylation of 7 CpGs; only three CpGs were differentially methylated among males with no overlap of significant CpGs observed among females. Secondary analyses revealed several differentially methylated regions (DMRs) and CpG loci mapping to genes with key roles in psychiatric outcomes, social interaction, and cognition, as well as immunologic and metabolic phenotypes. While fluoride exposure may impact the epigenome during early adolescence, the functional consequences of these changes are unclear warranting further investigation.

The Pediatric Asthma Risk Score: More does not mean better

Asthma is a chronic inflammatory lung disease that affects 6.2 million children worldwide.1 The vast heterogeneity in endotypes makes it difficult to predict which children will develop asthma. The Pediatric Asthma Risk Score (PARS) is a quantitative risk score for asthma developed using clinical and demographic data that can be used by health care providers, parents, and researchers.2 PARS was developed using data from the Cincinnati Childhood Allergy and Air Pollution Study (CCAAPS) birth cohort3 to identify risk factors predicting asthma development at age 7 years.

Source Apportionment of Particulate Matter by Application of Machine Learning Clustering Algorithms

A source apportionment (SA) study was conducted on two PM2.5 data sets, two carbon fractions and eight temperature-resolved carbon fractions collected during Cincinnati Childhood Allergy and Air Pollution Study (CCAAPS). This study aimed to evaluate two clustering algorithms: k-means clustering (kMC) and spectral clustering (SC) as potential receptor models for source apportionment. The application of kMC produced unsatisfactory results, but the results obtained from SC demonstrated a significant correlation with the results obtained using positive matrix factorization (PMF). The clustering results obtained were associated with practical evidence available in the literature. SC identified six source factors on analyzing two carbon fractions data set and seven factors from eight temperature-resolved carbon fractions data set. The sources (source contribution in parentheses) identified are: combustion (45.9 ± 3.66%) and secondary sulfate (11.4 ± 1.09%), vegetative/wood burning (17.5 ± 1.46%), diesel (10.6 ± 0.92%) and gasoline (3.6 ± 0.33%) vehicles, soil/crustal (2.07 ± 0.2%), traffic (9.3 ± 0.81%), and metal processing (8.8 ± 0.72%). The source profiles obtained using SC also show similarity with the profiles derived using PMF. In summary, this study presented a basic framework for applying Machine Learning algorithms for SA analysis. Also, it presents SC as a potential receptor model technique for SA.

Residential bacteria and fungi identified by high-throughput sequencing and childhood respiratory health

The objective of this study was to examine and compare environmental microbiota from dust and children's respiratory health outcomes at ages seven and twelve. At age seven, in-home visits were conducted for children enrolled in the Cincinnati Childhood Allergy and Air Pollution Study (CCAAPS). Floor dust was collected and analyzed for bacterial (16S rRNA gene) and fungal (internal transcribed spacer region) microbiota. Respiratory outcomes, including physician-diagnosed asthma, wheeze, rhinitis, and aeroallergen sensitivity were assessed by physical examination and caregiver-report at ages seven and twelve. The associations between dust microbiota and respiratory outcomes were evaluated using Permanova, DESeq, and weighted quantile sum (WQS) regression models. Four types of WQS regression models were run to identify mixtures of fungi or bacteria that were associated with the absence or presence of health outcomes. For alpha or beta diversity of fungi and bacteria, no significant associations were found with respiratory health outcomes. DESeq identified specific bacterial and fungal indicator taxa that were higher or lower with the presence of different health outcomes. Most individual indicator fungal species were lower with asthma and wheeze and higher with aeroallergen positivity and rhinitis, whereas bacterial data was less consistent. WQS regression models demonstrated that a combination of species might influence health outcomes. Several heavily weighted species had a strong influence on the models, and therefore, created a microbial community that was associated with the absence or presence of asthma, wheeze, rhinitis, and aeroallergen+. Weights for specific species within WQS regression models supported indicator taxa findings. Health outcomes might be more influenced by the composition of a complex mixture of bacterial and fungal species in the indoor environment than by the absence or presence of individual species. This study demonstrates that WQS is a useful tool in evaluating mixtures in relation to potential health effects.

Fluoride exposure during early adolescence and its association with internalizing symptoms

BackgroundEarly, chronic, low-level fluoride exposure has been linked to attention-deficit hyperactivity disorder (ADHD) and learning deficits in children. Rodent studies suggest a link between fluoride exposure and internalizing behaviors. No human studies have examined the impact of fluoride on internalizing behaviors during adolescence. ObjectiveEvaluate the relationship between urinary fluoride and early adolescent internalizing symptoms in the Cincinnati Childhood Allergy and Air Pollution Study (CCAAPS). MethodsParticipants in CCAAPS provided non-fasting spot urine samples at age 12 years (n = 286). Urine samples were analyzed using a microdiffusion method to determine childhood urinary fluoride (CUF) concentrations and were log-transformed for analyses. Caregivers of CCAAPS participants completed the Behavior Assessment System for Children-2 (BASC-2) at the age 12 study visit to assess internalizing symptoms (e.g., anxiety, depression, somatization), and a composite score of the three domains; T-scores ≥ 60 were used to identify adolescents in a clinically “at-risk” range. Race, age of the adolescent, household income, maternal age at birth, caregiver depression, caregiver-child relationships, and age 12-year serum cotinine concentrations were considered covariates in regression models. Sex-specific effects of fluoride exposures were investigated through the inclusion of interaction terms. ResultsHigher CUF concentrations were significantly associated with increased somatization (β = 3.64, 95% CI 0.49, 6.81) and internalizing composite T-scores in a clinically “at-risk” range (OR = 2.9, 95% CI 1.24, 6.9). Compared to females, males with higher CUF concentrations had more internalizing (pinteraction = 0.04) and somatization symptoms (pinteraction = 0.02) and were nearly seven times more likely to exhibit “at-risk” internalizing symptomology. CUF concentrations were not significantly associated with depression or anxiety symptoms. ConclusionsThis is the first study to link fluoride exposure and internalizing symptoms, specifically somatization. Somatization represents an interface of physical and psychological health. Continued follow-up will help shed light on the sex-specific relationship between fluoride and mental health and the role of somatization.

Fluoride exposure and internalizing symptoms in adolescents in a United States cohort

BACKGROUND AND AIM: Studies have shown a relationship between early chronic, low-level fluoride exposure and attention-deficit hyperactivity disorder and learning abilities in children. Animal studies suggest a link between fluoride exposure and internalizing behaviors. No human studies have examined the impact of fluoride on internalizing behaviors during adolescence. METHODS: Participants enrolled in the Cincinnati Childhood Allergy and Air Pollution Study (CCAAPS) provided non-fasting spot urine samples at age 12 (n=286). Urine samples were analyzed using a microdiffusion method to determine childhood urinary fluoride (CUF) concentrations. Caregivers of CCAAPS participants completed the Behavior Assessment System for Children-2 at the age 12 study visit to assess symptoms of anxiety, depression, and somatization in their children. Race, age of the child, household income, maternal age at birth, caregiver depression, caregiver-child relationships, and age 12-year serum cotinine levels were considered covariates in linear regression models. Sex-specific effects of fluoride exposures were investigated through the inclusion of interaction terms. RESULTS:We observed a positive, significant association between CUF concentrations and increased somatization (β = 3.64, 95% CI 0.49, 6.81) and a positive, but not statistically significant, association with the internalizing composite scale (β = 2.64, 95% CI -0.15, 5.44). Significant sex differences were also observed; compared to females, males with higher CUF levels exhibited a greater degree of internalizing (pinteraction=0.04) and somatization behaviors (pinteraction=0.02). No associations between urinary fluoride levels and depressive symptoms were found. CONCLUSIONS:This is the first study to examine fluoride concentrations in urine collected during adolescence and internalizing symptoms, specifically somatization, with males being more at risk. Somatization straddles the interface between physical and psychological health and is often comorbid with anxiety and depression. This was a cross-sectional study; therefore, continued follow-up will help shed light on the impact of fluoride exposure on mental health in children. KEYWORDS: children’s environmental health, fluoride, mental health outcomes

Environmental Exposure to Traffic Pollution and Motor Function in Adolescence

BACKGROUND AND AIM: Evidence supports the neurotoxic effects of air pollution on cognitive deficits, mental health, and behavioral outcomes in children. While heavy metal exposure has been associated with poor motor function, it is unclear whether traffic-related air pollution (TRAP) has a similar relationship. METHODS: Participants (n=332) were part of the Cincinnati Childhood Allergy and Air Pollution Study (CCAAPS). Elemental carbon attributable to traffic (ECAT), a marker of TRAP, was estimated at birth, age 12 years (current), and average exposure throughout childhood, using a validated land use regression model. Motor function was assessed with the Grooved Pegboard (GPB) test including time required to complete the task for dominant and non-dominant hand and number of dropped pegs. Associations between TRAP exposure and motor outcomes were estimated using linear (i.e., seconds to completion) and logistic (i.e, drops) regression; sex-specific effects were examined. Primary models controlled for child’s IQ, neighborhood deprivation, and total household income; secondary models included blood metals (i.e., lead, cadmium, mercury) collected at the age 12 visit. RESULTS:Children exposed to elevated current ECAT levels took on average 18 seconds longer to complete the GPB task with their non-dominant hand (95% CI 4.77, 31.14, p=0.008); ECAT was not associated with dominant hand completion. We did not observe a main effect of ECAT at any time point on probability of dropped pegs; however, girls exposed to higher childhood ECAT levels were more likely to drop pegs with their dominant hand during the GPB task (Psex*childhood ECAT = 0.03). Additionally controlling for heavy metal exposure did not alter the results. CONCLUSIONS:Higher TRAP exposure was associated with poorer motor function, and girls may be at increased risk for adverse outcomes. These findings, as well as others, suggest that air pollution is quickly becoming one of the leading threats to a child’s neurodevelopment. KEYWORDS: Children's environmental health, Neurodevelopmental outcomes, Traffic-related, Air pollution

Residential surrounding greenness and self-reported symptoms of anxiety and depression in adolescents

BackgroundEvidence on the relationship between exposure to greenness and adolescent mental health is limited. The purpose of this study was to examine the association between greenness throughout childhood and mental health at age 12 years. MethodsWe assessed greenness using the satellite-based measure of Normalized Difference Vegetation Index (NDVI) within 200m, 400m, and 800m of home address at birth, age 12 years, and across childhood (averaged for each year from birth to age 12) among the Cincinnati Childhood Allergy and Air Pollution Study (CCAAPS) cohort. Self-reported symptoms of anxiety and depression were assessed at age 12 years using the Spence Children's Anxiety Scale (SCAS) and Children's Depression Inventory 2 (CDI 2), respectively. Associations were estimated using linear regression, adjusting for covariates including traffic-related air pollution, neurological hazard exposure, blood lead level, household income, and community deprivation. ResultsIn adjusted models, NDVI was largely not associated with self-reported anxiety and depression symptoms, except for the SCAS separation anxiety subscale at 400m and 800m (0.1 unit increase mean NDVI 400m: β = −0.97, 95% CI: −1.86, −0.07; 800m: β = −1.33, 95% CI: −2.32, −0.34). ConclusionWhile we found no direct relationship between greenness and overall symptoms of anxiety and depression in adolescents upon adjustment for relevant covariates at the 200m distance, greenness may lesson symptoms of separation anxiety within 400m and 800m distance from the home address at age 12 years. Future research should examine mechanisms for these relationships at the community- and individual-level.

Residential Greenness, Asthma, and Lung Function in Young Children

Background. While benefits of greenness to health have been reported, studies specific to child respiratory health are scarce and findings are inconsistent. Objective. Exposure to greenness and respiratory outcomes were examined among the Cincinnati Childhood Allergy and Air Pollution Study (CCAAPS) cohort from birth to age 7 years. Methods. Residential surrounding greenness was averaged using the Normalized Difference Vegetation Index (NDVI) within 200, 400, and 800 meter distances from the home address at birth, age 7 years, and cumulative exposure across childhood (averaged for each year from birth to age 7 years). Respiratory outcomes were assessed at age 7 years, including lung function [percent predicted FEV1 (%FEV1), percent predicted FVC (%FVC), and percent predicted FEV1/FVC (%FEV1/FVC)] and asthma. The associations of a 0.1 unit increase in NDVI with respiratory outcomes were assessed using linear and logistic regression models adjusted for community deprivation, household income, and traffic-related air pollution. Results. Mean NDVI was significantly higher among children without asthma compared to those with asthma at birth in 200 meter and 800 meter distances from the home, and across childhood 200 meters from the home. No relationship was observed between NDVI at any age or buffer distance and asthma after adjustment. NDVI was significantly positively correlated with %FEV1 and %FVC for all distances at age 7 years and across childhood, and at 800 meters at birth. After adjustment, NDVI at age 7 years was significantly associated with %FEV1 (200 meters: β=2.05, 95% CI: [0.08, 3.3]; 400 meters: β=1.64, 95% CI: [0.3, 2.9]) and %FVC (200 meters: β=1.84, 95% CI: [0.7, 3.0]; 400 meters: β=1.55, 95% CI: [0.3, 2.8]; 800 meters: β=1.45, 95% CI: [0.1, 2.8]). No relationship was found between greenness and %FEV1/FVC. Conclusions. Greenness may not increase risk for child asthma, but may be beneficial to concurrent lung function.

Early-life exposure to traffic-related air pollution and child anthropometry.

Early-life exposure to traffic-related air pollution may decrease fetal growth and increase childhood obesity risk. Our objective was to evaluate the relationship of early-life exposure to traffic-related air pollution with birthweight in term newborns and obesity at age 7-8 years in two prospective birth cohorts in Cincinnati, OH (the Health Outcomes and Measures of the Environment (HOME) Study and Cincinnati Childhood Allergy and Air Pollution Study (CCAAPS)). We estimated elemental carbon attributable to traffic (ECAT) exposure at residential addresses during pregnancy with a validated land use regression model. We assessed birthweight among term infants using birth records or parent report (HOME Study n= 333 and CCAAPS n=590). We measured children's weight and height at 7-8 years, and calculated age- and sex-specific BMI z-scores (HOME Study n= 198 and CCAAPS n=459). Using multivariable linear regression, we estimated the difference in term birthweight and BMI z-score per interquartile range (IQR) increase in ECAT concentrations in each cohort separately and in the pooled sample. In adjusted models, ECAT exposure was not associated with lower birthweight (pooled sample β: 30g; 95% CI: -6, 66), or with higher BMI z-score (pooled sample β: -0.04; 95% CI: -0.15, 0.08). Infant sex modified the association between ECAT and birthweight (p=0.05). Among male newborns, higher ECAT concentrations were associated with higher birthweight (β: 61g; 95% CI: 9, 113), but we observed no association among female newborns (β: -9g; 95% CI: -58, 41). In contrast to some prior studies, early-life traffic-related air pollution exposure was not associated with lower birthweight or increased childhood adiposity in these two cohorts.

Asthma as an outcome: Exploring multiple definitions of asthma across birth cohorts in the Environmental influences on Child Health Outcomes Children's Respiratory and Environmental Workgroup

Asthma definitions vary widely across research studies and feature a trade-off between inclusivity and precision. Harmonizing definitions across multiple asthma birth cohort studies highlights these challenges.

Myo-inositol mediates the effects of traffic-related air pollution on generalized anxiety symptoms at age 12 years

BackgroundExposure to traffic-related air pollution (TRAP) has been linked to childhood anxiety symptoms. Neuroimaging in patients with anxiety disorders indicate altered neurochemistry. ObjectivesEvaluate the impact of TRAP on brain metabolism and its relation to childhood anxiety symptoms in the Cincinnati Childhood Allergy and Air Pollution Study (CCAAPS). MethodsAdolescents (n = 145) underwent magnetic resonance spectroscopy. Brain metabolites, including myo-inositol, N-acetylaspartate, creatine, choline, glutamate, glutamate plus glutamine, and glutathione were measured in the anterior cingulate cortex. Anxiety symptoms were assessed using the Spence Children's Anxiety Scale. TRAP exposure in early-life, averaged over childhood, and during the 12 months prior to imaging was estimated using a validated land use regression model. Associations between TRAP exposure, brain metabolism, and anxiety symptoms were estimated using linear regression and a bootstrapping approach for testing mediation by brain metabolite levels. ResultsRecent exposure to high levels of TRAP was associated with significant increases in myo-inositol (β = 0.26; 95%CI 0.01, 0.51) compared to low TRAP exposure. Recent elevated TRAP exposure (β = 4.71; 95% CI 0.95, 8.45) and increased myo-inositol levels (β = 2.98; 95% CI 0.43, 5.52) were also significantly associated with increased generalized anxiety symptoms with 12% of the total effect between TRAP and generalized anxiety symptoms being mediated by myo-inositol levels. ConclusionsThis is the first study of children to utilize neuroimaging to link TRAP exposure, metabolite dysregulation in the brain, and generalized anxiety symptoms among otherwise healthy children. TRAP may elicit atypical excitatory neurotransmission and glial inflammatory responses leading to increased metabolite levels and subsequent anxiety symptoms.

Identification of Two Early Life Eczema and Non-Eczema Phenotypes With High Risk For Asthma Development

Background The march has been considered a linear progression starting with eczema and culminating with development of asthma. Not all asthma cases, however, are preceded by eczema, and not all children with eczema go on to develop asthma. Objective The aim of this study was to explore the impact of allergic sensitization patterns on the association between early eczema and later childhood asthma. Given the numerous reported associations of the ciliary gene KIF3A with the atopic march, we also examined the impact of KIF3A risk allele rs12186803 on our analyses. Methods We studied 505 participants in the Cincinnati Childhood Allergy and Air Pollution Study (CCAAPS), a prospective birth cohort, with longitudinal eczema and asthma outcomes as well as prospective data regarding timing of sensitization to foods and aeroallergens. KIF3A genotypes were available on all children. Results Two high-risk groups were identified: one with and one without early eczema. The high-risk group with early eczema was more likely to be sensitized to food allergens, while the group without early eczema was more likely to be polysensitized to aeroallergens. The KIF3A rs12186803 risk allele interacted with food sensitization to increase asthma risk in children with eczema (P = 0.02). In children without eczema, asthma was associated with the interaction between rs12186803 and aeroallergen sensitization (P = 0.007). Conclusions & clinical relevance KIF3A interacted differentially with sensitization pattern to increase the risk of asthma in two high-risk groups of children with and without early eczema. Given the reported role of KIF3A in epithelial cell functioning, the results add evidence to the hypothesis that an impaired epithelial barrier is a key aspect in the development of allergic disease.

Exposure assessment models for elemental components of particulate matter in an urban environment: A comparison of regression and random forest approaches

Exposure assessment for elemental components of particulate matter (PM) using land use modeling is a complex problem due to the high spatial and temporal variations in pollutant concentrations at the local scale. Land use regression (LUR) models may fail to capture complex interactions and non-linear relationships between pollutant concentrations and land use variables. The increasing availability of big spatial data and machine learning methods present an opportunity for improvement in PM exposure assessment models. In this manuscript, our objective was to develop a novel land use random forest (LURF) model and compare its accuracy and precision to a LUR model for elemental components of PM in the urban city of Cincinnati, Ohio. PM smaller than 2.5 μm (PM2.5) and eleven elemental components were measured at 24 sampling stations from the Cincinnati Childhood Allergy and Air Pollution Study (CCAAPS). Over 50 different predictors associated with transportation, physical features, community socioeconomic characteristics, greenspace, land cover, and emission point sources were used to construct LUR and LURF models. Cross validation was used to quantify and compare model performance. LURF and LUR models were created for aluminum (Al), copper (Cu), iron (Fe), potassium (K), manganese (Mn), nickel (Ni), lead (Pb), sulfur (S), silicon (Si), vanadium (V), zinc (Zn), and total PM2.5 in the CCAAPS study area. LURF utilized a more diverse and greater number of predictors than LUR and LURF models for Al, K, Mn, Pb, Si, Zn, TRAP, and PM2.5 all showed a decrease in fractional predictive error of at least 5% compared to their LUR models. LURF models for Al, Cu, Fe, K, Mn, Pb, Si, Zn, TRAP, and PM2.5 all had a cross validated fractional predictive error less than 30%. Furthermore, LUR models showed a differential exposure assessment bias and had a higher prediction error variance. Random forest and other machine learning methods may provide more accurate exposure assessment.

Clinical and Environmental Factors Associated with Habitual Snoring in the Cincinnati Childhood Allergy and Air Pollution Study (CCAAPS)

Clinical and Environmental Factors Associated with Habitual Snoring in the Cincinnati Childhood Allergy and Air Pollution Study (CCAAPS)

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.

Aeroallergen Wheal Area Especially for Molds At Ages Two and Three Predicts Allergic Rhinitis At Age Four: The Cincinnati Childhood Allergy and Air Pollution Study (CCAAPS)

Aeroallergen Wheal Area Especially for Molds At Ages Two and Three Predicts Allergic Rhinitis At Age Four: The Cincinnati Childhood Allergy and Air Pollution Study (CCAAPS)

House dust bioactivities predict skin prick test reactivity for children with high risk of allergy

Although evidence suggests that ambient exposures to endotoxin and other immunostimulants during early life influence allergic risk, efforts to understand this host-environment relationship have been hampered by a paucity of relevant assays. These investigations determined whether parameters of house dust extract (HDE) bioactivity were predictive of allergen skin prick test (SPT) reactivity for infants at high risk of allergy participating in the Cincinnati Childhood Allergy and Air Pollution Study (CCAAPS). We conducted a nested case-control study, selecting 99 CCAAPS children who had positive SPT results to at least 1 aeroallergen at age 3 years and 101 subjects with negative SPT results. HDEs were prepared from dust samples collected from the subjects' homes at age 1 year. Murine splenocytes and bone marrow-derived dendritic cells were incubated with HDEs, and supernatant cytokine concentrations were determined by means of ELISA. Alternatively, bone marrow-derived dendritic cells were preincubated with HDEs, and then LPS-induced IL-6 responses were assessed. HDE endotoxin levels were determined by using the limulus amebocyte lysate assay. HDEs derived from the homes of children with positive (cases) and negative (control subjects) SPT results had similar bioactivities. However, when cases were considered in isolation, HDEs with higher levels of bioactivity were significantly associated with children who had lower numbers of positive SPT results. Analogous statistical analyses did not identify any association between HDE endotoxin levels and the aeroallergen sensitization profiles of children included in this study. HDE immunostimulatory activities predicted the aeroallergen sensitization status of CCAAPS subjects better than HDE endotoxin levels. These results provide the first published evidence that HDE bioassays have clinical relevance in predicting atopic risk.

Diesel Exhaust Exposure, Wheezing and Sneezing

The rising incidence of allergic disorders in developed countries is unexplained. Exposure to traffic related air pollutants may be an important cause of wheezing and asthma in childhood. Experimental evidence from human studies suggests that diesel exhaust particles, constituents of fine particulate matter less than 2.5 microns (PM2.5), may act to enhance IgE mediated aeroallergen sensitization and Th2 directed cytokine responses. To date, epidemiologic investigations indicate that children living in close proximity to heavily travelled roads are more likely to be atopic and wheeze. The Cincinnati Childhood Allergy and Air Pollution Study (CCAAPS) birth cohort study was initiated to test the hypothesis that early high exposure to traffic related air pollutants is associated with early aeroallergen sensitization and allergic respiratory phenotypes. Using an exposure cohort design, more than 700 infants born to atopic parents were recruited at age 1 living either less than 400 meters (high traffic pollutant exposure) or greater than 1,500 meters (low exposure) from a major road. Children were medically evaluated and underwent skin prick testing with aeroallergen at screening, and re-evaluated sequentially at ages 1, 2, 3, 4, and 7. In this study, both proximity and land use regression (LUR) models of traffic air pollutant exposure have been assessed. Proximity to stop and go traffic with large concentrations of bus and truck traffic predicted persistent wheezing during infancy. The LUR model estimated elemental carbon attributable to traffic (ECAT) as a proxy for diesel exhaust particulate exposure. High ECAT was significantly associated with wheezing at age 1 as well as persistent wheezing at age 3. High mold exposure predicted a well defined asthma phenotype at age 7.

Chemical compositions and source identification of PM 2.5 aerosols for estimation of a diesel source surrogate

Exposure to traffic-related pollution during childhood has been associated with asthma exacerbation, and asthma incidence. The objective of the Cincinnati Childhood Allergy and Air Pollution Study (CCAAPS) is to determine if the development of allergic and respiratory disease is associated with exposure to diesel engine exhaust particles. A detailed receptor model analyses was undertaken by applying positive matrix factorization (PMF) and UNMIX receptor models to two PM 2.5 data sets: one consisting of two carbon fractions and the other of eight temperature-resolved carbon fractions. Based on the source profiles resolved from the analyses, markers of traffic-related air pollution were estimated: the elemental carbon attributed to traffic (ECAT) and elemental carbon attributed to diesel vehicle emission (ECAD). Application of UNMIX to the two data sets generated four source factors: combustion related sulfate, traffic, metal processing and soil/crustal. The PMF application generated six source factors derived from analyzing two carbon fractions and seven factors from temperature-resolved eight carbon fractions. The source factors (with source contribution estimates by mass concentrations in parentheses) are: combustion sulfate (46.8%), vegetative burning (15.8%), secondary sulfate (12.9%), diesel vehicle emission (10.9%), metal processing (7.5%), gasoline vehicle emission (5.6%) and soil/crustal (0.7%). Diesel and gasoline vehicle emission sources were separated using eight temperature-resolved organic and elemental carbon fractions. Application of PMF to both datasets also differentiated the sulfate rich source from the vegetative burning source, which are combined in a single factor by UNMIX modeling. Calculated ECAT and ECAD values at different locations indicated that traffic source impacts depend on factors such as traffic volumes, meteorological parameters, and the mode of vehicle operation apart from the proximity of the sites to highways. The difference in ECAT and ECAD, however, was less than one standard deviation. Thus, a cost benefit consideration should be used when deciding on the benefits of an eight or two carbon approach.