Jeff Burkle

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.

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.

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.

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.

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

To cite this article: Brunst KJ, Ryan PH, Lockey JE, Bernstein DI, McKay RT, Khurana Hershey GK, Villareal M, Biagini Myers JM, Levin L, Burkle J, Evans S, LeMasters GK. Unraveling the relationship between aeroallergen sensitization, gender, second‐hand smoke exposure, and impaired lung function. Pediatric Allergy Immunology 2012: 23: 479–487.

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.

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

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.

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

Abstract 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.

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. HighlightsThe long‐term health consequences of environmental exposure to Libby amphibole asbestos (LAA) occurring during childhood has not been investigated thoroughly.Previous studies of LAA exposure have relied on qualitative and semi‐quantitative approaches to characterizing exposure for use in health studies.Neither pleural nor interstitial changes were observed on x‐ray or HRCT.Significant associations were observed between childhood LAA exposure and respiratory symptoms during young adulthood. Pleuritic chest pain, reported by 23% of the cohort, has been previously identified as an early symptom associated with LAA exposure and warrants continued follow‐up of this population and others environmentally exposed to LAA.