Airway transcriptome networks identify susceptibility to frequent asthma exacerbations in children.

BACKGROUND: Frequent asthma exacerbators, defined as those experiencing more than 1 hospitalization in a year for an asthma exacerbation, represent an important subgroup of individuals with asthma. However, this group remains poorly defined and understudied in children. OBJECTIVE: Our aim was to determine the molecular mechanisms underlying asthma pathogenesis and exacerbation frequency. METHODS: We performed RNA sequencing of upper airway cells from both frequent and nonfrequent exacerbators enrolled in the Ohio Pediatric Asthma Repository. RESULTS: Through molecular network analysis, we found that nonfrequent exacerbators display an increase in modules enriched for immune system processes, including type 2 inflammation and response to infection. In contrast, frequent exacerbators showed expression of modules enriched for nervous system processes, such as synaptic formation and axonal outgrowth. CONCLUSION: These data suggest that the upper airway of frequent exacerbators undergoes peripheral nervous system remodeling, representing a novel mechanism underlying pediatric asthma exacerbation.

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 (16 S 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.

Mortality of workers employed in refractory ceramic fiber manufacturing: An update.

This study evaluates the possible association between refractory ceramic fiber (RCF) exposure and all causes of death. Current and former employees (n = 1,119) hired from 1952 to 1999 at manufacturing facilities in New York (NY) state and Indiana were included. Work histories and quarterly plant-wide sampling from 1987 to 2015 provided cumulative fiber exposure (CFE) estimates. The full cohort was evaluated as well as individuals with lower and higher exposure, <45 and ≥45 fiber-months/cc. The Life-Table-Analysis-System was used for all standardized mortality rates (SMRs). Person-years at risk were accumulated from start of employment until 12/31/2019 or date of death. There was no significant association with all causes, all cancers, or lung cancer in any group. In the higher exposed, there was a significant elevation in both malignancies of the "urinary organs" (SMR = 3.59, 95% confidence interval [CI] 1.44, 7.40) and "bladder or other urinary site" (SMR = 4.04, 95% CI 1.10, 10.36), which persisted in comparison to regional mortality rates from NY state and Niagara County. However, six of the nine workers with urinary cancers were known smokers. In the lower exposed, there was a significant elevation in malignancies of the lymphatic and hematopoietic system (SMR = 2.54, 95% CI 1.27, 4.55) and leukemia (SMR = 4.21, 95% CI 1.69, 8.67). There was one pathologically unconfirmed mesothelioma death. A second employee currently living with a pathologically confirmed mesothelioma was identified, but the SMR was non-significant when both were included in the analyses. The association of these two mesothelioma cases with RCF exposure alone is unclear because of potential past exposure to asbestos.

Pilot study on the efficiency of water-only decontamination for firefighters' turnout gear.

Firefighters are exposed to toxic environments upon entering burning structures. Many structures contain synthetic materials which release toxic chemicals when on fire. These chemicals can enter the body through multiple routes of exposure, including inhalation and skin absorption. Thus, according to the fire departments included in this study, firefighters now conduct on-site decontamination procedures to remove hazardous chemicals, including polycyclic aromatic hydrocarbons (PAHs) from the surface of firefighter turnout gear. Several methods are being practiced at the local level, including decontamination with soap and water, and decontamination with water alone. The water-only decontamination method requires less time and supplies yet has not been investigated as a suitable method for removing polycyclic aromatic hydrocarbons from turnout gear. Therefore, we evaluated the efficiency of this method by measuring PAH concentration levels before and after water-only decontamination. The calculated efficiency displays the percentage of PAHs removed (or not removed) at post-decontamination in relation to the initial sample collected at pre-decontamination. The turnout gear was sampled after live residential structure fires. Firefighter turnout gear was worn throughout Attack, Overhaul Search and Rescue, and Rescue from Fire operations. All firefighters came to a central location for sampling after completing their job responsibilities. Water only decontamination did not appear to be effective, resulting in an overall 42% increase in PAH contamination. The unexpected increase may have been due to disparate pre- and post-decontamination sampling sites on turnout gear.

Childhood exposure to Libby amphibole asbestos and respiratory health in young adults.

OBJECTIVES: Vermiculite ore containing Libby amphibole asbestos (LAA) was mined in Libby, MT, from the 1920s-1990. Recreational and residential areas in Libby were contaminated with LAA. This objective of this study was to characterize childhood exposure to LAA and investigate its association with respiratory health during young adulthood. METHODS: Young adults who resided in Libby prior to age 18 completed a health and activity questionnaire, pulmonary function testing, chest x-ray and HRCT scan. LAA exposure was estimated based on participant report of engaging in activities with potential LAA exposure. Quantitative LAA estimates for activities were derived from sampling data and literature reports. RESULTS: A total of 312 participants (mean age 25.1 years) were enrolled and reported respiratory symptoms in the past 12 months including pleuritic chest pain (23%), regular cough (17%), shortness of breath (18%), and wheezing or whistling in the chest (18%). Cumulative LAA exposure was significantly associated with shortness of breath (aOR = 1.12, 95% CI 1.01-1.25 per doubling of exposure). Engaging in recreational activities near Rainy Creek Road (near the former mine site) and the number of instances heating vermiculite ore to make it expand or pop were also significantly associated with respiratory symptoms. LAA exposure was not associated with pulmonary function or pleural or interstitial changes on either chest x-ray or HRCT. CONCLUSIONS: Pleural or interstitial changes on x-ray or HRCT were not observed among this cohort of young adults. However, childhood exposure to LAA was significantly associated with respiratory symptoms during young adulthood. Pleuritic chest pain, in particular, has been identified as an early symptom associated with LAA exposure and therefore warrants continued follow-up given findings of progressive disease in other LAA exposed populations.

A 30-year mortality and respiratory morbidity study of refractory ceramic fiber workers.

AIM: Report mortality (n = 1119), cancer incidence (n = 1207) and radiographic (n = 1451) findings from a 30-year investigation of current and former refractory ceramic fiber (RCF) workers. METHODS: Cause of death, health and work histories, radiographs and spirometry were collected. Mortality and cancer incidence were analyzed. Logistic regression analysis investigated the associations of latency and cumulative fiber exposure (CFE) on radiographic changes. RESULTS: The mortality study showed no increase in standardized mortality rates (SMR) for lung cancer, but urinary cancers were significantly elevated in the higher exposed group (SMR = 3.62, 95% CI: 1.33-7.88) and leukemia in the total cohort (SMR = 2.51, 95% CI: 1.08-4.94). One death attributed to mesothelioma was identified (SMR = 2.86, 95% CI: 0.07-15.93) in a worker reporting some asbestos exposure. The overall rate of pleural changes was 6.1%, attaining 21.4% in the highest CFE category for all subjects (adjusted odds ratio (aOR) = 6.9, 95% CI: 3.6-13.4), and 13.0% for those with no reported asbestos exposure (OR= 9.1, 95% CI: 2.5-33.6). Prevalence for recent hires (≥1985) was similar to the background. Interstitial changes were not elevated. Localized pleural thickening was associated with small decreases in spirometry results. CONCLUSION: Increases in leukemia and urinary cancer but not lung cancer mortality were found. One death attributed to mesothelioma was observed in a worker with self-reported asbestos exposure and a work history where occupational asbestos exposure may have occurred, rendering uncertainties in assigning causation. Radiographic analyses indicated RCF exposure alone is associated with increased pleural but not interstitial changes. Reductions in RCF exposure should continue. The mortality study is ongoing.

Traffic pollution is associated with early childhood aeroallergen sensitization.

BACKGROUND: No large, prospective, epidemiologic study has investigated the association between diesel exhaust particle (DEP) exposure and early aeroallergen sensitization and allergic rhinitis (AR) at 4 years of age. OBJECTIVE: To determine how exposure to traffic exhaust during infancy is associated with aeroallergen sensitization and AR at 4 years of age and the predictive utility of the wheal area at 1 to 3 years of age on AR at 4 years of age. METHODS: Infants born to aeroallergen sensitized parents were evaluated annually with skin prick tests to 15 aeroallergens with measurement of wheal areas. At 4 years of age, AR was defined as at least one positive aeroallergen skin prick test result and the presence of sneezing and a runny nose without a cold or flu. Infant (DEP) exposure was estimated using data from 27 air sampling monitors and a land use regression model. RESULTS: Complete data were available for 634 children at 4 years of age. Prevalence of AR increased annually from 6.9% to 21.9%. A positive trend was observed for high DEP exposure and aeroallergen sensitization at 2 and 3 years of age (odds ratio, 1.40; 95% confidence interval, 0.97-2.0) and (odds ratio, 1.35; 95% confidence interval, 0.98-1.85) but not with AR. At 2 years of age, every 1-mm(2) increase in the wheal area of timothy and Alternaria significantly increased the odds of AR at 4 years of age. At 3 years of age, every 1-mm(2) increase in the wheal area of fescue, dog, and Penicillium significantly increased the odds of AR at 4 years of age. CONCLUSION: DEP exposure enhances the risk of early aeroallergen sensitization. Aeroallergen wheal area at 2 and 3 years of age is associated with AR at 4 years of age.

Early-life mold and tree sensitivity is associated with allergic eosinophilic rhinitis at 4 years of age.

BACKGROUND: Nasal eosinophils are a biomarker for allergic rhinitis (AR) and are associated with increased symptom severity. OBJECTIVE: To identify predictors of allergic eosinophilic rhinitis (AER) in early childhood in children at higher risk for chronic allergic respiratory disorders. METHODS: In the Cincinnati Childhood Allergy and Air Pollution Study, infants born to aeroallergen-sensitized and symptomatic parents were examined and underwent skin prick testing (SPT) annually to 15 aeroallergens from 1 to 4 years of age. Wheal circumferences were traced and scanned and areas were determined by computer planimetry. At 4 years, AER was defined as (1) at least 1 positive aeroallergen SPT result, (2) presence of sneezing and runny nose without a cold or influenza, and (3) nasal eosinophilia of at least 5%. Wheal areas at 1 to 3 years were analyzed for an association with AER compared with children without AR. RESULTS: At 4 years, 487 children completed rhinitis health histories, SPT, and nasal sampling. Ninety-nine children (22.8%) had AR. Thirty-eight children had AER (8.8% of total sample and 38.4% of AR sample, respectively). At 3 years, for every 1-mm(2) increase in Penicillium species (adjusted odds ratio 1.18, 95% confidence interval 1.06-1.32, P = .002) and maple (adjusted odds ratio 1.07, 95% confidence interval 1.01-1.13, P = .02), wheal area significantly increased the risk of AER at 4 years of age. CONCLUSION: Allergic eosinophilic rhinitis was identified in 8.8% of children at 4 years of age. Age 3 years was the earliest that aeroallergen SPT wheal areas were predictive of AER. Skin testing at 3 years identifies children at risk for an AR phenotype with nasal eosinophilia.

Child and Adolescent Manganese Biomarkers and Adolescent Postural Balance in Marietta CARES Cohort Participants.

BACKGROUND: Manganese (Mn) plays a significant role in both human health and global industries. Epidemiological studies of exposed populations demonstrate a dose-dependent association between Mn and neuromotor effects ranging from subclinical effects to a clinically defined syndrome. However, little is known about the relationship between early life Mn biomarkers and adolescent postural balance. OBJECTIVES: This study investigated the associations between childhood and adolescent Mn biomarkers and adolescent postural balance in participants from the longitudinal Marietta Communities Actively Researching Exposures Study (CARES) cohort. METHODS: Participants were recruited into CARES when they were 7-9 y old, and reenrolled at 13-18 years of age. At both time points, participants provided samples of blood, hair, and toenails that were analyzed for blood Mn and lead (Pb), serum cotinine, hair Mn, and toenail Mn. In adolescence, participants completed a postural balance assessment. Greater sway indicates postural instability (harmful effect), whereas lesser sway indicates postural stability (beneficial effect). Multivariable linear regression models were conducted to investigate the associations between childhood and adolescent Mn biomarkers and adolescent postural balance adjusted for age, sex, height-weight ratio, parent/caregiver intelligence quotient, socioeconomic status, blood Pb, and serum cotinine. RESULTS: CARES participants who completed the adolescent postural balance assessment (n=123) were 98% White and 54% female and had a mean age of 16 y (range: 13-18 y). In both childhood and adolescence, higher Mn biomarker concentrations were significantly associated with greater adolescent sway measures. Supplemental analyses revealed sex-specific associations; higher childhood Mn biomarker concentrations were significantly associated with greater sway in females compared with males. DISCUSSION: This study found childhood and adolescent Mn biomarkers were associated with subclinical neuromotor effects in adolescence. This study demonstrates postural balance as a sensitive measure to assess the association between Mn biomarkers and neuromotor function. https://doi.org/10.1289/EHP13381.

Unraveling the relationship between aeroallergen sensitization, gender, second-hand smoke exposure, and impaired lung function.

BACKGROUND: Contradictory findings on the differential effects of second-hand smoke (SHS) on lung function in girls and boys may result from masked relationships between host and environmental factors. Allergic sensitization may augment the relationship between SHS and decreased lung function, although its role in relation to the inconsistent gender differences in children has not been elucidated. HYPOTHESIS: We hypothesize that there will be differences between boys and girls related to early-life allergic sensitization and exposure to SHS on pulmonary function later in childhood. METHODS: Participants in this study (n = 486) were drawn from the Cincinnati Childhood Allergy and Air Pollution (CCAAPS) birth cohort study consisting of 46% girls. Allergic sensitization was assessed by skin prick test (SPT) to 15 aeroallergens at ages 2, 4, and 7, while pulmonary function and asthma diagnosis occurred at age 7. SHS exposure was measured by hair cotinine at ages 2 and/or 4. Gender differences of SHS exposure on pulmonary function among children with positive SPTs at ages 2, 4, and 7 as well as first- and higher-order interactions were examined by multiple linear regression. Interactions significant in the multivariate models were also examined via stratification. Comparisons within and between stratified groups were assessed by examining the slope of the parameter estimates/beta coefficients and associated p-values and confidence intervals. RESULTS: Increased cotinine levels were significantly associated with decreases in FEV(1) (-0.03 l, p < 0.05), peak expiratory flow (-0.07 l/s, p < 0.05), and FEF (25-75%) (-0.06 l/s, p < 0.01). The interaction between cotinine and sensitization at age 2 was borderline significant (p = 0.10) in the FEF(25-75%) model and showed an exposure response effect according to the number of positive SPTs at age 2; zero (-0.06 l/s, p < 0.01), one (-0.09 l/s, p < 0.05), or two or more positive SPTs (-0.30 l/s, p < 0.01). Despite increased polysensitization among boys, the association between cotinine and FEF(25-75%) among girls, with two or more positive SPTs at age 2, showed the greatest deficits in FEF(25-75%) (-0.34 l/s vs. -0.05 l/s and -0.06 l/s for non-sensitized girls and boys, respectively. Girls with two or more positive SPTs showed a twofold greater decrease in FEF(25-5%) (-0.34 l/s; 95% CI: -0.55, -0.13) compared to boys with the same degree of allergic sensitization (-0.18 l/s; 95% CI: -0.41, 0.06), although this difference was not statistically significant. CONCLUSIONS: Reductions in lung function were observed among children exposed to SHS, and the number of aeroallergen-positive SPTs at age 2 modifies this relationship. Girls experiencing early childhood allergic sensitization and high SHS exposure are at greater risk of decreased lung function later in childhood compared to non-sensitized girls and boys and demonstrate greater deficits compared to boys with similar degrees of sensitization.

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.

Associations of observed home dampness and mold with the fungal and bacterial dust microbiomes.

The objective of this analysis was to examine and compare quantitative metrics of observed dampness and mold, including visible mold and moisture damage, and fungal and bacterial microbiomes. In-home visits were conducted at age 7 for children enrolled in the Cincinnati Childhood Allergy and Air Pollution Study. Trained study staff evaluated the primary residence and measured total areas of visible moisture and mold damage in the home. Floor dust was collected and archived. Archived dust samples collected from each home (n = 178) were extracted and analyzed using bacterial (16S rRNA gene) and fungal (internal transcribed spacer region) sequencing. Fungi were also divided into moisture requirement categories of xerophiles, mesophiles, and hydrophiles. Data analyses used Spearman's correlation, Kruskal-Wallis, Permanova, DESeq, and negative binomial regression models. Comparing high moisture or mold damage to no damage, five fungal species and two bacterial species had higher concentrations (absolute abundance) and six fungal species and three bacterial species had lower concentrations. Hydrophilic and mesophilic fungi showed significant dose-related increases with increasing moisture damage and mold damage, respectively. When comparing alpha or beta diversity of fungi and bacteria across mold and moisture damage levels, no significant associations or differences were found. Mold and moisture damage did not affect diversity of fungal and bacterial microbiomes. Instead, both kinds of damage were associated with changes in species composition of both bacterial and fungal microbiomes, indicating that fungal and bacterial communities in the home might be influenced by one another as well as by mold or moisture in the home.

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.

Quantitative and semiquantitative estimates of mold exposure in infancy and childhood respiratory health.

BACKGROUND: Previous epidemiologic studies of dampness and mold relied on metrics that did not fully assess exposure-response relationships. Our objective was to examine quantitative metrics of dampness and mold during infancy and respiratory health outcomes during childhood. METHODS: In-home visits were conducted before age 1 for children in the Cincinnati Childhood Allergy and Air Pollution Study. Respiratory outcomes included age 3 wheeze and age 7 asthma and wheeze. The associations between home exposure and respiratory outcomes were evaluated for 779 children using logistic regression adjusting for household income, neighborhood socioeconomic status, and the presence of pests. RESULTS: Children residing in homes with ≥0.29 m2 of moisture damage were significantly more likely to have wheezing at age 3 and persistent wheeze through age 7 (adjusted odds ratio [aOR] = 2.2; 95% confidence interval [CI] = 1.0, 4.3 and aOR = 3.2; CI = 1.3, 7.5, respectively). Additionally, homes having ≥0.19 m2 of mold damage were associated with wheezing at age 3 and early transient wheeze assessed at age 7 (aOR = 2.9; CI = 1.3, 6.4 and aOR = 3.5; CI = 1.5, 8.2, respectively). Mold damage <0.19 m2 and moisture damage <0.29 m2 were not associated with health outcomes. Mold and moisture damage were also not associated with asthma. CONCLUSION: Our data indicate that only the highest categories analyzed for mold (≥0.19 m2) and moisture damage (≥0.29 m2) in homes at age 1 were significantly associated with wheeze at ages 3 and 7; however, data below these levels were too sparse to assess the shape of the relationship or explore potential health-relevant thresholds.

Public Participation in Air Sampling and Water Quality Test Kit Development to Enable Citizen Science.

BACKGROUND: Public participation in environmental data collection is a rapidly growing approach providing opportunity for hands-on public engagement in environmental field studies. This methodology is important when addressing community-identified exposure concerns. OBJECTIVES: Our goal was to establish an academic-community partnership between University of Cincinnati (UC) researchers and local officials and residents of Guernsey County, Ohio, to address their interest in assessing environmental quality near proposed and operating natural gas extraction (NGE) waste sites. METHODS: A pilot research study was developed using community-based participatory research principles. A community resident was trained to collect air samples. Air was sampled at 10 locations for 63 volatile organic compounds (VOCs). Water quality test kits were developed in partnership with local middle and high school teachers. RESULTS: Community partners were involved throughout the project. VOCs were detected at all locations. Nineteen unique VOCs were detected; one was above the recommended exposure level. Findings were reported back to local officials and community members. Water quality test kits were developed and then piloted in middle school and high school classrooms. CONCLUSIONS: Academic-community partnerships were instrumental in the identification of sampling locations, obtaining the participation of landowners, and conducting sampling. Measuring the impact of NGE activities on air quality is challenging owing to competing exposures, limited resources, and access to sites. Water quality test kits were found by Guernsey County teachers to be useful tools in the classroom.

A land-use regression model for estimating microenvironmental diesel exposure given multiple addresses from birth through childhood.

The Cincinnati Childhood Allergy and Air Pollution Study (CCAAPS) is a prospective birth cohort whose purpose is to determine if exposure to high levels of diesel exhaust particles (DEP) during early childhood increases the risk for developing allergic diseases. In order to estimate exposure to DEP, a land-use regression (LUR) model was developed using geographic data as independent variables and sampled levels of a marker of DEP as the dependent variable. A continuous wind direction variable was also created. The LUR model predicted 74% of the variability in sampled values with four variables: wind direction, length of bus routes within 300 m of the sample site, a measure of truck intensity within 300 m of the sampling site, and elevation. The LUR model was subsequently applied to all locations where the child had spent more than eight hours per week from through age three. A time-weighted average (TWA) microenvironmental exposure estimate was derived for four time periods: 0-6 months, 7-12 months, 13-24 months, 25-36 months. By age two, one third of the children were spending significant time at locations other than home and by 36 months, 39% of the children had changed their residential addresses. The mean cumulative DEP exposure estimate increased from age 6 to 36 months from 70 to 414 microg/m3-days. Findings indicate that using birth addresses to estimate a child's exposure may result in exposure misclassification for some children who spend a significant amount of time at a location with high exposure to DEP.

Secondhand smoke and traffic exhaust confer opposing risks for asthma in normal and overweight children.

OBJECTIVE: Exposure to ultrafine particles (UFP) in secondhand smoke (SHS) and traffic-related air pollution (TRAP) may elicit chronic inflammation. It was hypothesized that the association between these exposures would be potentiated in overweight versus normal-weight children. METHODS: Average lifetime exposure to TRAP and SHS and objective, physician-diagnosed asthma were determined for 575 children at age 7. Overweight was defined as having a body mass index (BMI) >85th percentile for age and gender. The association between TRAP and SHS exposure and asthma was examined by logistic regression stratified by BMI. RESULTS: A total of 131 children were overweight; the prevalence of asthma was 24.4% and 14.2% among overweight and normal-weight children, respectively. Exposure to SHS was significantly associated with asthma among overweight (adjusted odds ratio [adjOR] = 3.0; 95% confidence interval [CI] = 1.2, 7.4) but not normal-weight children (adjOR = 1.1; 95% CI = 0.4, 2.7). In contrast, TRAP was significantly associated with asthma among normal-weight (adjOR = 1.8; 95% CI = 1.0, 3.4) but not overweight children (adjOR = 0.7; 95% CI = 0.4, 2.7). CONCLUSIONS: The association between SHS and TRAP exposure and asthma is modified by children's weight. Children's time-activity patterns, including time spent indoors or outdoors, may vary by weight and play an important role in these UFP exposures.

Genetic and environmental risk factors for childhood eczema development and allergic sensitization in the CCAAPS cohort.

Eczema is very common and increasing in prevalence. Prospective studies investigating environmental and genetic risk factors for eczema in a birth cohort are lacking. We evaluated risk factors that may promote development of childhood eczema in the Cincinnati Childhood Allergy and Air Pollution Study (CCAAPS) birth cohort (n=762) of infants with at least one atopic parent. Objective environmental exposure data were available for each participant. At annual physical examinations, children underwent skin prick tests (SPTs), eczema was diagnosed by a clinician, and DNA was collected. Among Caucasian children, 39% developed eczema by age 3. Children with a pet dog were significantly less likely to have eczema at age one (odds ratio (OR)=0.62, 95% confidence interval (CI): 0.40-0.97) or at both ages 2 and 3 (OR=0.54, 95% CI: 0.30-0.97). This finding was most significant among children carrying the CD14-159C/T CC genotype. Carriers of the CD14-159C/T and IL4Ralpha I75V single-nucleotide polymorphisms (SNPs) had an increased risk of eczema at both ages 2 and 3 (OR=3.44, 95% CI: 1.56-7.57), especially among children who were SPT+. These results provide new insights into the pathogenesis of eczema in high-risk children and support a protective role for early exposure to dog, especially among those carrying the CD14-159C/T SNP. The results also demonstrate a susceptibility effect of the combination of CD14 and IL4Ralpha SNPs with eczema.

High prevalence of aeroallergen sensitization among infants of atopic parents.

OBJECTIVE: To present methodology to identify atopic parents and determine the prevalence of sensitization to 15 aeroallergens in their infant offspring. STUDY DESIGN: A birth cohort of infants was identified from birth records; an infant was enrolled if 1 of the parents reported allergy respiratory symptoms and had a positive skin prick test (SPT) to a common aeroallergen. At age 1 year, these infants were tested to the same aeroallergens. RESULTS: Of the 680 enrolled infants, 28.4% were SPT+ to 1 or more aeroallergens and/or food, and 18.0% were positive to 1 or more aeroallergens. By category of allergens, 9.7% were sensitized to pollens, 7.5% to molds, 4.3% to house dust mite and/or cockroach, and 3.4% to dog and/or cat. Of the infants who were positive to an aeroallergen, 65.7% remained positive at age 2 years. CONCLUSIONS: Infants born to atopic parents with percutaneous sensitization to aeroallergens are at increased risk for aeroallergen sensitization during infancy, which persists to age 2 years. These findings suggest that current clinical practices, which generally avoid skin testing before age 2 years, be reassessed in this population of high-risk children.

Is it traffic type, volume, or distance? Wheezing in infants living near truck and bus traffic.

BACKGROUND: Previous studies of air pollution have not examined the association between exposure to varying types, distance, and amounts of traffic and wheezing in very young infants. OBJECTIVE: We sought to determine the relationship between types of traffic, traffic volume, and distance and wheezing among infants less than 1 year of age. METHODS: A geographic information system and a classification scheme were developed to categorize infants enrolled in the study as living near moving truck and bus traffic (highway >50 miles per hour, >1000 trucks daily, <400 m), stop-and-go truck and bus traffic (<50 miles per hour, <100 m), or unexposed and not residing near either. Symptom data were based on health questionnaires administered to parents when the infants were 6 months of age and monthly health diaries. RESULTS: Infants living very near (<100 m) stop-and-go bus and truck traffic had a significantly increased prevalence of wheezing (adjusted odds ratio, 2.50; 95% CI, 1.15-5.42) when compared with unexposed infants. The prevalence of wheezing among nonwhite infants was at least twice that of white infants, regardless of exposure. Infants living less than 400 m from a high volume of moving traffic, however, did not have an increased prevalence of wheezing. CONCLUSION: These results suggest that the distance from and type of traffic exposures are more significant risk factors than traffic volume for wheezing in early infancy.