Patrick H. Ryan

A Review of Land-use Regression Models for Characterizing Intraurban Air Pollution Exposure

Epidemiologic studies of air pollution require accurate exposure assessments at unmonitored locations in order to minimize exposure misclassification. One approach gaining considerable interest is the land-use regression (LUR) model. Generally, the LUR model has been utilized to characterize air pollution exposure and health effects for individuals residing within urban areas. The objective of this article is to briefly summarize the history and application of LUR models to date outlining similarities and differences of the variables included in the model, model development, and model validation. There were 6 studies available for a total of 12 LUR models. Our findings indicated that among these studies, the four primary classes of variables used were road type, traffic count, elevation, and land cover. Of these four, traffic count was generally the most important. The model R2 explaining the variability in the exposure estimates for these LUR models ranged from.54 to.81. The number of air sampling sites generating the exposure estimates, however, was not correlated with the model R2 suggesting that the locations of the sampling sites may be of greater importance than the total number of sites. The primary conclusion of this study is that LUR models are an important tool for integrating traffic and geographic information to characterize variability in exposures.

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.

Diesel exhaust particle induction of IL-17A contributes to severe asthma

BACKGROUND IL-17A has been implicated in severe forms of asthma. However, the factors that promote IL-17A production during the pathogenesis of severe asthma remain undefined. Diesel exhaust particles (DEPs) are a major component of traffic-related air pollution and are implicated in asthma pathogenesis and exacerbation. OBJECTIVE We sought to determine the mechanism by which DEP exposure affects asthma severity using human and mouse studies. METHODS BALB/c mice were challenged with DEPs with or without house dust mite (HDM) extract. Airway inflammation and function, bronchoalveolar lavage fluid cytokine levels, and flow cytometry of lung T cells were assessed. The effect of DEP exposure on the frequency of asthma symptoms and serum cytokine levels was determined in children with allergic asthma. RESULTS In mice exposure to DEPs alone did not induce asthma. DEP and HDM coexposure markedly enhanced airway hyperresponsiveness compared with HDM exposure alone and generated a mixed T(H)2 and T(H)17 response, including IL-13(+)IL-17A(+) double-producing T cells. IL-17A neutralization prevented DEP-induced exacerbation of airway hyperresponsiveness. Among 235 high DEP-exposed children with allergic asthma, 32.2% had more frequent asthma symptoms over a 12-month period compared with only 14.2% in the low DEP-exposed group (P = .002). Additionally, high DEP-exposed children with allergic asthma had nearly 6 times higher serum IL-17A levels compared with low DEP-exposed children. CONCLUSIONS Expansion of T(H)17 cells contributes to DEP-mediated exacerbation of allergic asthma. Neutralization of IL-17A might be a useful potential therapeutic strategy to counteract the asthma-promoting effects of traffic-related air pollution, especially in highly exposed patients with severe allergic asthma.

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.

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.

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 childs exposure may result in exposure misclassification for some children who spend a significant amount of time at a location with high exposure to DEP.

Role of Financial and Social Hardships in Asthma Racial Disparities

BACKGROUND AND OBJECTIVES: Health care reform offers a new opportunity to address child health disparities. This study sought to characterize racial differences in pediatric asthma readmissions with a focus on the potential explanatory role of hardships that might be addressed in future patient care models. METHODS: We enrolled 774 children, aged 1 to 16 years, admitted for asthma or bronchodilator-responsive wheezing in a population-based prospective observational cohort. The outcome was time to readmission. Child race, socioeconomic status (measured by lower income and caregiver educational attainment), and hardship (caregivers looking for work, having no one to borrow money from, not owning a car or home, and being single/never married) were recorded. Analyses used Cox proportional hazards. RESULTS: The cohort was 57% African American, 33% white, and 10% multiracial/other; 19% were readmitted within 12 months. After adjustment for asthma severity classification, African Americans were twice as likely to be readmitted as whites (hazard ratio: 1.98; 95% confidence interval: 1.42 to 2.77). Compared with whites, African American caregivers were significantly more likely to report lower income and educational attainment, difficulty finding work, having no one to borrow money from, not owning a car or home, and being single/never married (all P ≤ .01). Hardships explained 41% of the observed racial disparity in readmission; jointly, socioeconomic status and hardship explained 49%. CONCLUSIONS: African American children were twice as likely to be readmitted as white children; hardships explained >40% of this disparity. Additional factors (eg, pollution, tobacco exposure, housing quality) may explain residual disparities. Targeted interventions could help achieve greater child health equity.

Visually observed mold and moldy odor versus quantitatively measured microbial exposure in homes

The main study objective was to compare different methods for assessing mold exposure in conjunction with an epidemiologic study on the development of childrens asthma. Homes of 184 children were assessed for mold by visual observations and dust sampling at childs age 1 (Year 1). Similar assessment supplemented with air sampling was conducted in Year 7. Samples were analyzed for endotoxin, (1-3)-β-D-glucan, and fungal spores. The Mold Specific Quantitative Polymerase Chain Reaction assay was used to analyze 36 mold species in dust samples, and the Environmental Relative Moldiness Index (ERMI) was calculated. Homes were categorized based on three criteria: 1) visible mold damage, 2) moldy odor, and 3) ERMI. Even for homes where families had not moved, Year 7 endotoxin and (1-3)-β-d-glucan exposures were significantly higher than those in Year 1 (p<0.001), whereas no difference was seen for ERMI (p=0.78). Microbial concentrations were not consistently associated with visible mold damage categories, but were consistently higher in homes with moldy odor and in homes that had high ERMI. Low correlations between results in air and dust samples indicate different types or durations of potential microbial exposures from dust vs. air. Future analysis will indicate which, if any, of the assessment methods is associated with the development of asthma.