Surrogate Measure Of Exposure Research Articles

Bladder cancer and occupational exposure to metalworking fluid mist: a counter-matched case–control study in French steel-producing factories

ObjectivesTo assess the relationship between occupational exposure to metalworking fluids (MWFs) in the steel-producing industry and bladder cancer incidence.MethodsA nested case–control study on bladder cancer was set up in a...

Assessing Exposure to Household Air Pollution: A Systematic Review and Pooled Analysis of Carbon Monoxide as a Surrogate Measure of Particulate Matter.

Background:Household air pollution from solid fuel burning is a leading contributor to disease burden globally. Fine particulate matter () is thought to be responsible for many of these health impacts. A co-pollutant, carbon monoxide (CO) has been widely used as a surrogate measure of in studies of household air pollution.Objective:The goal was to evaluate the validity of exposure to CO as a surrogate of exposure to in studies of household air pollution and the consistency of the relationship across different study settings and conditions.Methods:We conducted a systematic review of studies with exposure and/or cooking area and CO measurements and assembled 2,048 and CO measurements from a subset of studies (18 cooking area studies and 9 personal exposure studies) retained in the systematic review. We conducted pooled multivariate analyses of associations, evaluating fuels, urbanicity, season, study, and CO methods as covariates and effect modifiers.Results:We retained 61 of 70 studies for review, representing 27 countries. Reported correlations (r) were lower for personal exposure (range: 0.22–0.97; ) than for cooking areas (range: 0.10–0.96; ). In the pooled analyses of personal exposure and cooking area concentrations, the variation in ln(CO) explained 13% and 48% of the variation in ln(), respectively.Conclusions:Our results suggest that exposure to CO is not a consistently valid surrogate measure of exposure to . Studies measuring CO exposure as a surrogate measure of PM exposure should conduct local validation studies for different stove/fuel types and seasons. https://doi.org/10.1289/EHP767

3D conformal radiotherapy is not associated with the long-term cardiac mortality in breast cancer patients: a retrospective cohort study in Germany (PASSOS-Heart Study).

In breast cancer patients treated in the 1970s and 1980s, radiation therapy (RT) for left-sided tumors has been associated with an elevated risk of cardiac mortality. In recent years, improved RT techniques have reduced radiation exposure of the heart and major coronary vessels, but some exposure remains unavoidable. In a retrospective cohort study, we investigated the long-term cardiac mortality risk of breast cancer survivors treated with modern RT in Germany. A total of 11,982 women were included who were treated for breast cancer between 1998 and 2008. A systematic mortality follow-up was conducted until December 2012. The effect of breast cancer laterality on cardiac mortality and on overall mortality was investigated as a surrogate measure of exposure. Using Cox regression, we analyzed survival time as the primary outcome measure, taking potential confounding factors into account. We found no evidence for an effect of tumor laterality on mortality in irradiated patients (N=9058). For cardiac mortality, the hazard ratio was 0.94 (95% CI 0.64-1.38) for left-sided versus right-sided tumors. For all causes of death, the hazard ratio was 0.95 (95% CI 0.85-1.05). A diagnosis of cardiac illness prior to breast cancer treatment increased both cardiac mortality risk and overall mortality risk. Contemporary RT seems not to be associated with an increased risk of cardiac mortality or overall mortality for left-sided breast cancer relative to right-sided RT. However, an extended follow-up period and exact dosimetry might be necessary to confirm this observation.

Creation of a retrospective job-exposure matrix using surrogate measures of exposure for a cohort of US career firefighters from San Francisco, Chicago and Philadelphia

ObjectivesTo construct a cohort-specific job-exposure matrix (JEM) using surrogate metrics of exposure for a cancer study on career firefighters from the Chicago, Philadelphia and San Francisco Fire Departments.MethodsDepartmental work history...

Circulating estrogens and estrogens within the breast among postmenopausal BRCA1/2 mutation carriers.

Accurately quantifying parent estrogens (PE) estrone (E1) and estradiol (E2) and their metabolites (EM) within breast tissue and serum may permit detailed investigations of their contributions to breast carcinogenesis among BRCA1/2 mutation carriers. We conducted a study of PE/EM in serum, nipple aspirate fluid (NAF), and ductal lavage supernatant (DLS) among postmenopausal BRCA1/2 mutation carriers. PE/EM (conjugated and unconjugated) were measured in paired serum/NAF (n = 22 women) and paired serum/DLS samples (n = 24 women) using quantitative liquid chromatography-tandem mass spectrometry (LC/MS/MS). The relationships between serum and tissue-specific PE/EM were measured using Pearson's correlation coefficients. Conjugated forms of PE/EM constituted the majority of estrogen in serum (88 %), NAF (59 %) and DLS (69 %). PE/EM in NAF and serum were highly correlated [E1 (r = 0.97, p < 0.0001), E2 (r = 0.90, p < 0.0001) and estriol (E3) (r = 0.74, p < 0.0001)] as they were in DLS and serum [E1 (r = 0.92, p < 0.0001; E2 (r = 0.70, p = 0.0001; E3 (r = 0.67, p = 0.0004)]. Analyses of paired total estrogen values for NAF and serum, and DLS and serum yielded ratios of 0.22 (95 % CI 0.19-0.25) and 0.28 (95 % CI 0.24-0.32), respectively. This report is the first to employ LC/MS/MS to quantify PE/EM in novel breast tissue-derived biospecimens (i.e., NAF and DLS). We demonstrate that circulating PE and EM are strongly and positively correlated with tissue-specific PE and EM measured in NAF and DLS among postmenopausal BRCA1/2 mutation carriers. If confirmed, future etiologic studies could utilize the more readily obtainable serum hormone levels as a reliable surrogate measure of exposure at the tissue level.

Job duration as a surrogate measure of exposure to shiftwork in relation to mortality

ObjectivesHuman evidence of carcinogenicity concerning shiftwork is inconsistent. In a previous study, we found no effect on mortality in relation to ever / never working nightshift. The present analyses examined...

Personal PM2.5 Exposure Among Wildland Firefighters Working at Prescribed Forest Burns in Southeastern United States

This study investigated occupational exposure to wood and vegetative smoke in a group of 28 forest firefighters at prescribed forest burns in a southeastern U.S. forest during the winters of 2003–2005. During burn activities, 203 individual person-day PM2.5 and 149 individual person-day CO samples were collected; during non-burn activities, 37 person-day PM2.5 samples were collected as controls. Time-activity diaries and post-work shift questionnaires were administered to identify factors influencing smoke exposure and to determine how accurately the firefighters’ qualitative assessment estimated their personal level of smoke exposure with discrete responses: “none” or “very little,” “low,” “moderate,” “high,” and “very high.” An average of 6.7 firefighters were monitored per burn, with samples collected on 30 burn days and 7 non-burn days. Size of burn plots ranged from 1–2745 acres (avg = 687.8). Duration of work shift ranged from 6.8–19.4 hr (avg = 10.3 hr) on burn days. Concentration of PM2.5 ranged from 5.9–2673 μg/m3 on burn days. Geometric mean PM2.5 exposure was 280 μg/m3 (95% CL = 140, 557 μg/m3, n = 177) for burn day samples, and 16 μg/m3 (95% CL = 10, 26 μg/m3, n = 35) on non-burn days. Average measured PM2.5 differed across levels of the firefighters’ categorical self-assessments of exposure (p < 0.0001): none to very little = 120 μg/m3 (95% CL = 71, 203 μg/m3) and high to very high = 664 μg/m3 (95% CL = 373, 1185 μg/m3); p < 0.0001 on burn days). Time-weighted average PM2.5 and personal CO averaged over the run times of PM2.5 pumps were correlated (correlation coefficient estimate, r = 0.79; CLs: 0.72, 0.85). Overall occupational exposures to particulate matter were low, but results indicate that exposure could exceed the ACGIH®-recommended threshold limit value of 3 mg/m3 for respirable particulate matter in a few extreme situations. Self-assessed exposure levels agreed with measured concentrations of PM2.5. Correlation analysis shows that either PM2.5 or CO could be used as a surrogate measure of exposure to woodsmoke at prescribed burns.

Residential Density of Roadways Associated with Cough and Asthma in Urban Children through Age 5 Years

RATIONALE: Exposure to traffic-related air pollution has been associated with asthma and respiratory symptoms in children. However, the effects of lifetime exposures are not well-characterized. We aimed to use geographic indicators of traffic as surrogate measures of exposure to traffic-related air pollution and to characterize associations with asthma-related outcomes among New York City children through age 5 years.

Concentrations of selected organochlorines and chlorobenzenes in the serum of former Love Canal residents, Niagara Falls, New York ,☆,☆☆☆This study was approved by the New York State Department of Health Institutional Review Board as part of the larger Love Canal Follow-up Health Study (study #99-312) at a full board meeting in August 1996 and annually thereafter.

Love Canal, in Niagara Falls, NY is among the earliest and most significant hazardous waste sites in the USA, but no study has ever measured chemical body burdens in nearby residents to document that human exposure occurred. This study measured concentrations of selected organochlorines and chlorinated benzenes in archived serum samples collected from former Love Canal residents. We analyzed serum samples collected from 373 former residents in 1978-1979 for compounds disposed of at Love Canal, and we compared their concentrations according to surrogate indicators of exposure such as residential proximity, adjusting for potential confounders. Three compounds were detectable in the serum of most participants: 1,2,4-trichlorobenzene (1,2,4-TCB), beta-hexachlorocyclohexane (beta-HCH) and 1,2-dichlorobenzene (1,2-DCB). Concentrations of 1,2,4-TCB and 1,2-DCB were 2-14 times greater among persons who at the time their blood was collected lived closest to the Canal compared to those living further away. We found no consistent trends for beta-HCH with respect to any exposure definition. These results provide evidence that residential proximity to Love Canal contributed to the body burden of certain contaminants, and helps validate the use of surrogate exposure measures in health effect studies. Further surveillance of the Love Canal cohort is warranted.

An Evaluation of Surrogate Chemical Exposure Measures and Autism Prevalence in Texas

There is currently considerable discussion in the scientific community as well as within the general public concerning the role mercury (Hg) exposures may play in the apparent increased incidence of neurodevelopmental disorders (particularly autism) in children. Although the primary focus of this debate has focused on ethylmercury from vaccinations, linkage to other sources of Hg has been proposed. An ecologic association between 2001 Toxic Release Inventory (TRI; www.epa.gov/tri) data for Hg and 2000–2001 school district autism prevalence was previously reported in Texas. Evaluations using industrial release data as surrogate exposure measures may be problematic, particularly for chemicals like Hg that have complex environmental fates. To explore the robustness of TRI-based analyses of the Hg–autism hypothesis in Texas, a detailed analysis was undertaken examining the extent of the ecological relationship during multiple years and examining whether surrogate exposure measures would yield similar conclusions. Using multilevel Poisson regression analysis and data obtained from a number of publicly available databases, it was found that air Hg release data were significantly associated with autism prevalence in Texas school districts when considering data for 2001 and 2002 (2001: RR = 4.45, 95% CI = 1.60–12.36, 2002: RR = 2.70, 95% CI = 1.17–6.15). Significant associations were not found using data from 2003 to 2005. A significant association was not observed when considering air Hg data for 2000 or 2001 and school district autism prevalence data for 2005–2006 or 2006–2007, an analysis allowing for a 5-yr time period between presumed exposure and entry into the public school system (2000: RR = 1.03, 95% CI = 0.59–1.83, 2001: RR = 0.94, 95% CI = 0.59–1.47). Significant associations were not observed for any year nor for the time lagged analyses when censored autism counts were replaced by threes instead of zeros. An evaluation of TRI air emissions data for several other pollutants did not find significant associations except for nickel (RR = 1.71, 1.12–2.60), which has no history of being associated with neurodevelopmental disorders. An evaluation using downwind location from coal-fired power plants as the exposure surrogate variable also did not yield statistically significant results. The analysis suggests Hg emissions are not consistently associated with autism prevalence in Texas school districts. The lack of consistency across time may be the result of the influence of a more significant factor which remains unidentified. Alternatively, it may be that the significant association observed in 2001 and 2002 does not represent a true causal association.

Parent report of pests and pets and indoor allergen levels in inner-city homes

Guidelines recommend allergen avoidance for patients with allergic asthma, but direct measurements of home allergen levels are not available to most physicians. Parent report of indoor allergen exposure is a potentially convenient and inexpensive surrogate measure of exposure, although validity of parent report to estimate indoor allergen levels is not well established. To determine if parent-reported pest and pet exposures can identify patients with clinically relevant allergen exposure. Parents of 300 inner-city children completed a survey about pests (cockroaches and mice) and furred pets (dogs and cats). Settled dust samples were obtained for Bla g 1, Mus m 1, Can f 1, and Fel d 1 from kitchens and bedrooms. Parent reports were associated with clinically relevant levels of Bla g 1, Mus m 1, Can f 1, and Fel d 1 (P < .001 for all). For example, when parents reported cockroaches were present, 86% of homes had settled dust Bla g 1 levels of 1 U/g or higher, and when they reported mice were present, 90% had Mus m 1 levels greater than 500 ng/g. Report of pets was also predictive of clinically meaningful allergen levels. Parent-reported absence of pets provided assurance that allergen levels were below relevant thresholds (negative predictive value, 80%-98%). However, parent-reported absence of pests did not provide assurance of low levels of these allergens (negative predictive value, 38%-75%). Since direct measurement of indoor allergens is not always feasible, especially in the inner city, parent report of pests and pets may be sufficient to recommend environmental control practices for sensitized children. Negative parent reports of pests are not sufficient evidence of low pest allergen exposure.

Maximum likelihood, multiple imputation and regression calibration for measurement error adjustment

In epidemiologic studies of exposure-disease association, often only a surrogate measure of exposure is available for the majority of the sample. A validation sub-study may be conducted to estimate the relation between the surrogate measure and true exposure levels. In this article, we discuss three methods of estimation for such a main study/validation study design: (i) maximum likelihood (ML), (ii) multiple imputation (MI) and (iii) regression calibration (RC). For logistic regression, we show how each method depends on a different numerical approximation to the likelihood, and we adapt standard software to compute both MI and ML estimates. We use simulation to compare the performance of the estimators for both realistic and extreme settings, and for both internal and external validation designs. Our results indicate that with large measurement error or large enough sample sizes, ML performs as well as or better than MI and RC. However, for smaller measurement error and small sample sizes, either ML or RC may have the advantage. Interestingly, in most cases the relative advantage of RC versus ML was determined by the relative variance rather than the bias of the estimators. Software code for all three methods in SAS is provided.

Exposure assessment: implications for epidemiological studies of ionizing radiation

Quantitative estimates of ionizing radiation exposure are often available for use in epidemiological studies. However, depending on the context, the quality of the exposure estimates can vary. For example, the estimates may be specific to individuals in the study or generic values averaged over populations; unavailable for some of the potential study subjects or vary in their form between individuals; based on contemporary measurements or assessed retrospectively; based on measurements alone, on surrogate measures of exposure, or on an exposure assessment model; or, as is often the case, cover one source of radiation exposure rather than all of them. Various ways in which ionizing radiation exposures have been assessed are illustrated through reference to some studies of childhood leukaemia, concerning environmental, medical, natural and parental occupational exposures. Based on this, implications for the interpretation of radiation epidemiological studies are discussed.

QTF-Gold assay for monitoring of anti-tuberculosis therapy in subjects with active TB

Introduction: The identification and characterization of two M. tuberculosis-specific antigens (ESAT-6 and CFP- 10) has led to the development of a whole blood new generation of M. tuberculosis specific diagnostic tests, that have several advantages over tuberculin skin test (TST), in terms of higher specificity, better correlation with surrogate measures of exposure to M. tuberculosis in low-incidence setting, and less cross-reactivity with M. bovis (BCG) vaccine and environmental mycobacteria.The role of these new tests in evaluating post-therapy tuberculosis eradication has not been investigated yet. Aim of this longitudinal study was to determinate changes of response to M. tuberculosis-specific antigens in patients during the standard tuberculosis treatment and to investigate the in vitro effects of tuberculosis drugs on the IFN-γ release. Methods: 23 individuals with active tuberculosis were enrolled and followed over time.They were tested with QuantiFERON TB-Gold (QFT-Gold) at four time points: at diagnosis (t0), after 3 and 6 months of treatment (t1- t2) and at the end of the specific treatment (t3). Results: At baseline all patients were positive by QFT-Gold.At second time-point 17 out of 23 (74%) were positive, at third time-point 11 of 23 (47%) were positive, at treatment completion 3/23 (13%) were positive.The conversion to negative response to M. tuberculosis-specific antigens was found in 87% patients analyzed after successful therapy. Longitudinal QFT-Gold testing shown a significant decrease (p&lt;0.001) of IFN-γ response during the therapy. No inhibitory effect on IFN-γ release was noted in vitro for chemotherapy using at concentrations compatible with those achieved in serum of treated patients.We have revealed an inhibitory effect only at concentrations 2-3 times greater than those previously tested. Conclusion: A successful therapy for tuberculosis causes a significant decrease of the ESAT-6 and CFP-10 response and this data suggest that the QTF-Gold assay may have a role as a tool for evaluating tuberculosis eradication after standard tuberculosis treatment.

Frequency and patterns of contact with domestic poultry and potential risk of H5N1 transmission to humans living in rural Cambodia.

Background Since 2004, H5N1 outbreaks have been recurrent in domestic poultry and humans in Cambodia. To date, seven human cases (100% CFR) and 22 outbreaks in poultry have been confirmed. Household ownership of backyard poultry (FAO Sector 4 poultry production) in rural Cambodia is high. An understanding of the extent and frequency of poultry handing behaviors in these settings is necessary to assess the risk associated with different practices and to formulate sensible recommendations to mitigate this risk. We collected new data from six geographic regions to examine patterns of human contact with poultry among rural farmers in Cambodia and identify populations with the highest potential exposure to H5N1. Methods and Findings A cross‐sectional survey was undertaken in which 3,600 backyard poultry owners from 115 randomly selected villages in six provinces throughout Cambodia were interviewed. Using risk assessment methods, patterns of contact with poultry as surrogate measures of exposure to H5N1 were used to generate risk indices of potential H5N1 transmission to different populations in contact with poultry. Estimates of human exposure risk for each study participant (n = 3600) were obtained by multiplying each reported practice with a transmission risk‐weighting factor and summing these over all practices reported by each individual. Exposure risk estimates were then examined stratified by age and gender. Subjects reported high contact with domestic poultry (chickens and ducks) through the daily care and food preparation practices, however contact patterns varied by gender and age. Males between the ages of 26‐40 reported practices of contact with poultry that give rise to the highest H5N1 transmission risk potential, followed closely by males between the ages of 16‐25. Overall, males had a higher exposure risk potential than females across all age groups (p < 0·001). Conclusions Our results demonstrate that most of the population in rural Cambodia is in frequent contact with domestic poultry. About half of the population in this study carried out on a regular basis at least one of the practices considered to be high risk for the effective transmission if the bird is infected. There was however substantial variation in the frequency of different practices and thus the potential risk of transmission of H5N1 from poultry to humans is not uniform across age and gender even amongst populations living in close proximity to poultry.

Panel discussion review: session two — interpretation of observed associations between multiple ambient air pollutants and health effects in epidemiologic analyses

Air pollution epidemiologic research has often utilized ambient air concentrations measured from centrally located monitors as a surrogate measure of exposure to these pollutants. Associations between these ambient concentrations and health outcomes such as lung function, hospital admissions, and mortality have been examined in short- and long-term cohort studies as well as in time-series and case-crossover studies. The issues related to interpreting the observed associations of ambient air pollutants with health outcomes were discussed at the US EPA sponsored workshop on December 13 and 14, 2006 in Chapel Hill, North Carolina, USA. The second session of this workshop focused on the following topics: (1) statistical methodology and study designs that may improve understanding of multipollutant health effects; (2) ambient concentrations as surrogate measures of pollutant mixtures; and (3) source-focused epidemiologic research. New methodology and approaches to better distinguish the effects of individual pollutants include multicity hierarchical modeling and the use of case-crossover analysis to control for copollutants. An alternative approach is to examine the mixture as a whole using principal component analysis. Another important consideration is to what extent the observed health associations are attributable to individual pollutants, which are often from common sources and are correlated, versus the pollutant mixtures that the pollutants are representing. For example, several ambient air concentrations, such as particulate matter mass, nitrogen dioxide, and carbon monoxide, may be serving as surrogate measures of motor vehicle exhaust. Source apportionment analysis is one method that may allow further advancement in understanding the source components that contribute to multipollutant health effects.

Dependence of tar, nicotine and carbon monoxide yields on physical parameters: implications for exposure, emissions control and monitoring

Objective: To estimate the extent to which tar, nicotine and carbon monoxide (TNCO) yields are dependent on cigarette design features such as burn rate, filter ventilation and paper porosity, and...

Home use of margarine is an important determinant of plasma trans fatty acid status: a biomarker study

The contribution of the home use of margarines, made with partially hydrogenated vegetables oils, to total trans fatty acid intake is difficult to determine using dietary assessment because food composition databases are incomplete for trans fatty acids; moreover, hidden fats in manufactured foods may be the predominant sources of trans fatty acids. The objective of our study was to determine, using plasma phospholipid trans fatty acid composition as a surrogate measure of exposure, whether the home use of margarine or butter is an important determinant of trans fatty acid status. We conducted a community-based (Dunedin, New Zealand), cross-sectional survey of people who consumed either margarine (n 65) or butter (n 64) but not both for home use. The levels of the 18:1 trans isomers commonly found in partially hydrogenated vegetable oils were all significantly higher in the plasma phospholipids of margarine compared with butter consumers, with the exception of 18:1n-7t, which did not differ. Among margarine consumers, the percentage of total fat from margarine was significantly correlated with levels of phospholipid 18:1n-6t, 18:1n-8t and 18:1n-12/9t isomers (r 0.57-0.63, P<0.001) but only weakly with 18:1n-7t (r 0.30, P=0.016). The intake of fat from fast foods, bakery products or meat and meat products was not associated with plasma phospholipid trans isomeric composition. The home use of margarine, made with partially hydrogenated vegetable oils, is an important determinant of trans fatty acid exposure in New Zealand.

Proximity of schools in Detroit, Michigan to automobile and truck traffic

Exposure to traffic-related air pollutants, which has been associated with a range of adverse health effects, often is represented using indirect proxies or surrogate exposure measures, most commonly, the proximity to busy roads. This study examines the proximity of grade K-12 schools to high traffic roads in Wayne County, Michigan, an area including the industrialized city of Detroit as well as outlying urban and suburban communities. Unlike earlier studies, commercial and non-commercial traffic is distinguished, and effects of school type (public, charter, private), socio-economic variables, demographic factors, and mapping errors are evaluated. We find that total traffic flow, as measured by annual average daily traffic (AADT), does not reflect the substantial differences between trucking and commuting routes. Thus, AADT alone may inadequately capture traffic-related exposures, especially given the large differences between diesel and gasoline emissions. Based on close proximity (school-road distance < or = 150 m) to heavy traffic (AADT > or = 50,000), 4.9% of the 845 Wayne County schools are traffic exposed at school. In the urban core area, 7.2% of schools and 7.6% of students are traffic exposed at school. A larger proportion of grade 7-12 students in public schools are exposed than K-6 students. Considering truck emissions, 2.8% of the schools are within 150 m of roads with 5000 or more trucks per day. In Wayne County, students attending schools near high traffic roads are more likely to be Black or Hispanic, to be enrolled in a meal program, and to reside in a poor area. Many of these results are driven by the large minority population in the densely populated core area of Detroit. The findings show that a large fraction of children have high exposures to traffic-related pollutants, especially in Detroit, and the need for exposure measures that account for both the composition and volume of traffic.

Air samples versus biomarkers for epidemiology

Background: It has been speculated on theoretical grounds that biomarkers are superior surrogates for chemical exposures to air samples in epidemiology studies. Methods and Results: Biomarkers were classified according to...