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.

NAT1 genetic variation increases asthma risk in children with secondhand smoke exposure.

OBJECTIVE: We previously reported that children exposed to secondhand smoke (SHS) that carried variants in the NAT1 gene had over two-fold higher hair cotinine levels. Our objective was to determine if NAT1 polymorphisms confer increased risk for developing asthma in children exposed to SHS. METHODS: White participants in the Cincinnati Childhood Allergy and Air Pollution Study (n = 359) were genotyped for 10 NAT1 variants. Smoke exposure was defined by hair cotinine and parental report. Asthma was objectively assessed by spirometry and methacholine challenge. Findings were replicated in the Genomic Control Cohort (n = 638). RESULTS: Significant associations between 5 NAT1 variants and asthma were observed in the CCAAPS exposed group compared to none in the unexposed group. There was a significant interaction between NAT1 rs13253389 and rs4921581 with smoke exposure (p = 0.02, p = 0.01) and hair cotinine level (p = 0.048, p = 0.042). Children wildtype for rs4921581 had increasing asthma risk with increasing hair cotinine level, whereas those carrying the NAT1 minor allele had an increased risk of asthma regardless of cotinine level. In the GCC, 13 NAT1 variants were associated with asthma in the smoke-exposed group, compared to 0 in the unexposed group, demonstrating gene-level replication. CONCLUSIONS: Variation in the NAT1 gene modifies asthma risk in children exposed to secondhand-smoke. To our knowledge, this is the first report of a gene-environment interaction between NAT1 variants, smoke exposure, cotinine levels, and pediatric asthma. NAT1 genotype may have clinical utility as a biomarker of increased asthma risk in children exposed to smoke.

Respiratory follow-up pre- and post-engineering controls or cessation of added diacetyl at four microwave popcorn facilities.

In a 7-year study at 4 microwave popcorn facilities, mixing room employees exposed to diacetyl prior to the introduction of respirators showed significant loss of lung function but did not continue to decline longitudinally faster than other job categories http://bit.ly/2xwWRiw.

Using high-resolution residential greenspace measures in an urban environment to assess risks of allergy outcomes in children.

Despite reported health benefits of urban greenspace (gs), the epidemiological evidence is less clear for allergic disease. To address a limitation of previous research, we examined the associations of medium- and high-resolution residential gs measures and tree and/or grass canopies with allergic outcomes for children enrolled in the longitudinal cincinnati childhood allergy and air pollution study (ccaaps). We estimated residential gs based on 400 m radial buffers around participant addresses (n = 478) using the normalized differential vegetation index (ndvi) and land cover-derived urban greenspace (ugs) (tree and grass coverage, combined and separate) at 30 m and 1.5-2.5 m resolution, respectively. Associations between outdoor aeroallergen sensitization and allergic rhinitis at age 7 and residential gs measures at different exposure windows were examined using multivariable logistic regression models. A 10% increase in ugs-derived grass coverage was associated with an increased risk of sensitization to grass pollens (adjusted odds ratio [aor]: 1.27; 95% confidence interval = 1.02-1.58). For each 10% increase in ugs-derived tree canopy coverage, nonstatistically significant decreased odds were found for grass pollen sensitization, tree pollen sensitization, and sensitization to either (aor range = 0.87-0.94). Results similar in magnitude to ugs-tree canopy coverage were detected for ndvi and allergic sensitizations. High-resolution (down to 1.5 m) gs measures of grass- and tree-covered areas showed associations in opposite directions for different allergy outcomes. These data suggest that measures strongly correlated with tree canopy (e.g., ndvi) may be insufficient to detect health effects associated with proximity to different types of vegetation or help elucidate mechanisms related to specific gs exposure pathways.

A Pediatric Asthma Risk Score to better predict asthma development in young children.

BACKGROUND: Asthma phenotypes are currently not amenable to primary prevention or early intervention because their natural history cannot be reliably predicted. Clinicians remain reliant on poorly predictive asthma outcome tools because of a lack of better alternatives. OBJECTIVE: We sought to develop a quantitative personalized tool to predict asthma development in young children. METHODS: Data from the Cincinnati Childhood Allergy and Air Pollution Study (n = 762) birth cohort were used to identify factors that predicted asthma development. The Pediatric Asthma Risk Score (PARS) was constructed by integrating demographic and clinical data. The sensitivity and specificity of PARS were compared with those of the Asthma Predictive Index (API) and replicated in the Isle of Wight birth cohort. RESULTS: PARS reliably predicted asthma development in the Cincinnati Childhood Allergy and Air Pollution Study (sensitivity = 0.68, specificity = 0.77). Although both the PARS and API predicted asthma in high-risk children, the PARS had improved ability to predict asthma in children with mild-to-moderate asthma risk. In addition to parental asthma, eczema, and wheezing apart from colds, variables that predicted asthma in the PARS included early wheezing (odds ratio [OR], 2.88; 95% CI, 1.52-5.37), sensitization to 2 or more food allergens and/or aeroallergens (OR, 2.44; 95% CI, 1.49-4.05), and African American race (OR, 2.04; 95% CI, 1.19-3.47). The PARS was replicated in the Isle of Wight birth cohort (sensitivity = 0.67, specificity = 0.79), demonstrating that it is a robust, valid, and generalizable asthma predictive tool. CONCLUSIONS: The PARS performed better than the API in children with mild-to-moderate asthma. This is significant because these children are the most common and most difficult to predict and might be the most amenable to prevention strategies.

Comparison of digital and film chest radiography for detection and medical surveillance of silicosis in a setting with a high burden of tuberculosis.

BACKGROUND: Continuing use of analog film and digital chest radiography for screening and surveillance for pneumoconiosis and tuberculosis in lower and middle income countries raises questions of equivalence of disease detection. This study compared analog to digital images for intra-rater agreement across formats and prevalence of changes related to silicosis and tuberculosis among South African gold miners using the International Labour Organization classification system. METHODS: Miners with diverse radiological presentations of silicosis and tuberculosis were recruited. Digital and film chest images on each subject were classified by four expert readers. RESULTS: Readings of film and soft copy digital images showed no significant differences in prevalence of tuberculosis or silicosis, and intra-rater agreement across formats was fair to good. Hard copy images yielded higher prevalences. CONCLUSION: Film and digital soft copy images show consistent prevalence of findings, and generally fair to good intra-rater agreement for findings related to silicosis and tuberculosis.

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.

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.

Parental Snoring and Environmental Pollutants, but Not Aeroallergen Sensitization, Are Associated with Childhood Snoring in a Birth Cohort.

The objective of this study was to determine whether atopy and other clinical and environmental variables predict the risk of childhood habitual snoring (HS) in a birth cohort born to atopic parents. Participants completed clinical evaluations and questionnaires at ages 1-4 and age 7. HS was defined as snoring ≥3 nights/week. Traffic-related air pollution (TRAP) exposure was estimated using land-use regression. The association between early (≤age 4) and current (age 7) allergic disease, environmental exposures, and snoring at age 7 was examined using adjusted logistic regression. Of the 609 children analyzed the prevalence of HS at age 7 was 21%. Early tobacco smoke exposure [environmental tobacco smoke (ETS)] [odds ratio (OR) 1.79, 95% CI (confidence interval) 1.12-2.84], rhinitis (OR 1.74, 95% CI 1.06-2.92), wheezing (OR 1.63, 95% CI 1.05-2.53), maternal HS (OR 2.08, 95% CI 1.36-3.18), and paternal HS (OR 1.83, 95% CI 1.14-3.00) were significantly associated with HS at age 7. Current TRAP (OR 1.93, 95% CI 1.13-3.26), respiratory infections (OR 1.16, 95% 1.03-1.35), maternal HS (OR 2.86, 95% CI 1.69-4.84), and paternal HS (OR 3.01, 95% CI 1.82-5.09) were significantly associated with HS at age 7. To our knowledge, this is the largest birth cohort examining longitudinal predictors of snoring in children born to atopic parents. Parental HS was the only variable consistently associated with childhood HS from ages 1 to 7. Early rhinitis, early ETS exposure, and concurrent traffic pollution exposure increased the risk of HS at age 7, while aeroallergen sensitization did not. Children with these characteristics should be considered for screening of sleep disorders.

Allergic Diseases and Internalizing Behaviors in Early Childhood.

BACKGROUND AND OBJECTIVES: The relationship between allergic diseases and internalizing disorders has not been well characterized with regard to multiple allergic diseases or longitudinal study. The objective of this study was to examine the association between multiple allergic diseases in early childhood with validated measures of internalizing disorders in the school-age years. METHODS: Children enrolled in the Cincinnati Childhood Allergy and Air Pollution Study underwent skin testing and examinations at ages 1, 2, 3, 4, and 7 years. At age 7, parents completed the Behavior Assessment System for Children, Second Edition (BASC-2), a validated measure of childhood behavior and emotion. The association between allergic diseases at age 4, including allergic rhinitis, allergic persistent wheezing, atopic dermatitis, and allergic sensitization, and BASC-2 internalizing, anxiety, and depression T scores at age 7 was examined by logistic and linear regression, adjusting for covariates. RESULTS: The cohort included 546 children with complete information on allergic disease and BASC-2 outcomes. Allergic rhinitis at age 4 was significantly associated with elevated internalizing (adjusted odds ratio [aOR]: 3.2; 95% confidence interval [CI]: 1.8-5.8), anxiety (aOR: 2.0; 95% CI: 1.2-3.6), and depressive scores (aOR: 3.2; 95% CI: 1.7-6.5) at age 7. Allergic persistent wheezing was significantly associated with elevated internalizing scores (aOR: 2.7; 95% CI: 1.2-6.3). The presence of >1 allergic disease (aOR: 3.6; 95% CI: 1.7-7.6) and allergic rhinitis with comorbid allergic disease(s) (aOR: 4.3; 95% CI: 2.0-9.2) at age 4 had dose-dependent associations with internalizing scores. CONCLUSIONS: Children with allergic rhinitis and allergic persistent wheezing at age 4 are at increased risk of internalizing behaviors at age 7. Furthermore, multiple allergic diseases had a dose-dependent association with elevated internalizing scores.

Exposure to allergen and diesel exhaust particles potentiates secondary allergen-specific memory responses, promoting asthma susceptibility.

BACKGROUND: Exposure to traffic pollution particulate matter, predominantly diesel exhaust particles (DEPs), increases the risk of asthma and asthma exacerbation; however, the underlying mechanisms remain poorly understood. OBJECTIVE: We sought to examine the effect of DEP exposure on the generation and persistence of allergen-specific memory T cells in asthmatic patients and translate these findings by determining the effect of early DEP exposure on the prevalence of allergic asthma in children. METHODS: The effect of DEPs on house dust mite (HDM)-specific memory responses was determined by using an asthma model. Data from children enrolled in the Cincinnati Childhood Allergy and Air Pollution Study birth cohort were analyzed to determine the effect of DEP exposure on asthma outcomes. RESULTS: DEP coexposure with HDM resulted in persistent TH2/TH17 CD127(+) effector/memory cells in the lungs, spleen, and lymph nodes of adult and neonatal mice. After 7 weeks of rest, a single exposure to HDM resulted in airway hyperresponsiveness and increased TH2 cytokine levels in mice that had been previously exposed to both HDM and DEPs versus those exposed to HDM alone. On the basis of these data, we examined whether DEP exposure was similarly associated with increased asthma prevalence in children in the presence or absence of allergen exposure/sensitization in the Cincinnati Childhood Allergy and Air Pollution Study birth cohort. Early-life exposure to high DEP levels was associated with significantly increased asthma prevalence among allergic children but not among nonallergic children. CONCLUSION: These findings suggest that DEP exposure results in accumulation of allergen-specific TH2/TH17 cells in the lungs, potentiating secondary allergen recall responses and promoting the development of allergic asthma.

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.

HRCT/CT and associated spirometric effects of low Libby amphibole asbestos exposure.

OBJECTIVE: Evaluate the relationship between cumulative fiber exposure and high-resolution or conventional chest computed tomography (HRCT/CT) changes and spirometry of workers with Libby amphibole asbestos exposure. METHODS: Of the original 1980 cohort (n = 513), 431 were living and asked to participate. Images were evaluated for localized pleural thickening (LPT), diffuse pleural thickening (DPT), and parenchymal changes. RESULTS: A total of 306 participants provided either HRCT/CT scans (n = 191) or chest radiographs (n = 115). Of the 191 with HRCT/CT, 52.9% had pleural changes and 13.1% had parenchymal changes. Those with LPT only, LPT and/or DPT, or DPT and/or parenchymal changes had mean 6.1, 8.0, and 18.0 loss in percent predicted forced vital capacity, respectively. CONCLUSIONS: Exposure to vermiculite containing amphibole fibers is associated with pleural and parenchymal HRCT/CT changes at low cumulative fiber exposure; these changes are associated with spirometric decrements.

Isocyanates and human health: multistakeholder information needs and research priorities.

OBJECTIVES: To outline the knowledge gaps and research priorities identified by a broad base of stakeholders involved in the planning and participation of an international conference and research agenda workshop on isocyanates and human health held in Potomac, Maryland, in April 2013. METHODS: A multimodal iterative approach was used for data collection including preconference surveys, review of a 2001 consensus conference on isocyanates, oral and poster presentations, focused break-out sessions, panel discussions, and postconference research agenda workshop. RESULTS: Participants included representatives of consumer and worker health, health professionals, regulatory agencies, academic and industry scientists, labor, and trade associations. CONCLUSIONS: Recommendations were summarized regarding knowledge gaps and research priorities in the following areas: worker and consumer exposures; toxicology, animal models, and biomarkers; human cancer risk; environmental exposure and monitoring; and respiratory epidemiology and disease, and occupational health surveillance.

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.

Childhood exposure to Libby amphibole during outdoor activities.

Residents of Libby, MT were exposed to amphibole asbestos through multiple environmental pathways. Previous exposure characterization has primarily relied on qualitative report of these exposure activities. The objectives of this study were to describe available data from the US EPA preremediation actions for Libby amphibole (LA) exposure in Libby, MT and develop an approach to characterize outdoor residential exposure to LA among children. Homes in Libby, MT included in the US EPA preremediation Contaminant Screening Survey (CSS) were categorized by the presence of interior and/or exterior visible vermiculite and concentrations of LA were measured in samples of dust and soil. Airborne exposure to LA while digging/gardening, raking, and mowing were estimated using US EPA activity-based sampling (ABS) results. Residential histories and frequency/duration of childhood activities were combined with ABS to demonstrate the approach for estimating potential exposure. A total of 3154 residential properties participated in the CSS and 44% of these had visible exterior vermiculite. Airborne concentrations of LA where there was visible vermiculite outdoors were 3-15 times higher during digging/gardening, raking, and mowing activities compared with homes without visible outdoor vermiculite. Digging and gardening activities represented the greatest contribution to estimated exposures and 73% of the participants reported this activity before the age of 6 years. This methodology demonstrated the use of historical preremediation data to estimate residential exposures of children for specific activities. Children younger than age 6 years may have been exposed to LA while digging/gardening, especially at homes where there is visible outdoor vermiculite. This approach may be extended to other activities and applied to the entire cohort to examine health outcomes.