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Biomedical subjects

Dick Heederik

Publications and source records attributed to Dick Heederik.

17 recordsLinked to original sources

Mortality from obstructive lung diseases and exposure to polycyclic aromatic hydrocarbons among asphalt workers.

Work in the asphalt industry has been associated with nonmalignant respiratory morbidity and mortality, but the evidence is not consistent. A historical cohort of asphalt workers included 58,862 men (911,209 person-years) first employed between 1913 and 1999 in companies applying and mixing asphalt in Denmark, Finland, France, Germany, Israel, the Netherlands, and Norway. The relations between mortality from nonmalignant respiratory diseases (including the obstructive lung diseases: chronic bronchitis, emphysema, and asthma) and specific chemical agents and mixtures were evaluated using a study-specific exposure matrix. Mortality from obstructive lung diseases was associated with the estimated cumulative and average exposures to polycyclic aromatic hydrocarbons and coal tar (p values of the test for linear trend = 0.06 and 0.01, respectively). The positive association between bitumen fume exposure and mortality from obstructive lung diseases was weak and not statistically significant; confounding by simultaneous exposure to coal tar could not be excluded. The authors lacked data on smoking and full occupational histories. In conclusion, exposures to polycyclic aromatic hydrocarbons, originating from coal tar and possibly from bitumen fume, may have contributed to mortality from obstructive lung diseases among asphalt workers, but confounding and bias cannot be ruled out as an explanation for the observed associations.

Causality↗

Lung cancer mortality in a Dutch cohort of asphalt workers: evaluation of possible confounding by smoking.

BACKGROUND: Using data from a Dutch cohort of workers in road construction and asphalt mixing companies, this article describes possible confounding of the association between exposure to bitumen fume and lung cancer mortality by smoking. METHODS: A retrospective cohort of 3,714 workers with at least one season of employment was identified. Semi-quantitative exposure to bitumen fume was assessed by a job-exposure matrix. Information on smoking habits was available for a sub-cohort of 1,138 workers, who underwent medical examinations by the occupational health services in the past. RESULTS: Smoking habits differed between occupational title groups and there was a positive association between cumulative exposure and smoking. Internal analyses using the non-exposed subjects as reference category, showed a positive association between semi-quantitative bitumen fume exposure and lung cancer risk. After adjusting for differences in smoking habits, all relative risks were reduced, but a weak positive association could still be observed. CONCLUSION: Confounding by smoking on the association between exposure to bitumen fume and lung cancer mortality is possible, although the positive trend (not statistically significant) for lung cancer mortality remained. Only a nested case-control study may allow proper treatment of potential (residual) confounding by smoking in this population.

Adult↗

Performance of different exposure assessment approaches in a study of bitumen fume exposure and lung cancer mortality.

BACKGROUND: We compared performance of different exposure assessment approaches in a cohort study of cancer risk among European asphalt workers. METHODS: Three bitumen fume exposure indices (duration of exposure (years), average exposure (mg/m3) and cumulative exposure (mg/m3*years)) and two latency models (with and without a 15 year lag) were considered for an association between lung cancer mortality and bitumen fume. RESULTS: There was no association between lung cancer risk and either duration or cumulative exposure. However, there was the suggestion of an increase in lung cancer risk accompanying rise in average exposure. Only models with average bitumen fume exposure (with or without lag) improved model fit, albeit to the same extent. CONCLUSIONS: Constructing quantitative indices of exposure intensity was justified because they produced the greatest improvement in fit of models that explored possible relationship between bitumen fume exposure and lung cancer risk. The identified associations require further investigation.

Cohort Studies↗

Cancer mortality among European asphalt workers: an international epidemiological study. I. Results of the analysis based on job titles.

BACKGROUND: Inhalation of bitumen fumes is potentially carcinogenic to humans. METHODS: We conducted a study of 29,820 male workers exposed to bitumen in road paving, asphalt mixing and roofing, 32,245 ground and building construction workers unexposed to bitumen, and 17,757 workers not classifiable as bitumen workers, from Denmark, Finland, France, Germany, Israel, the Netherlands, Norway, and Sweden, with mortality follow-up during 1953-2000. We calculated standardized mortality ratios (SMRs) and 95% confidence intervals (CIs) based on national mortality rates. Poisson regression analyses compared mortality of bitumen workers to that of building or ground construction workers. RESULTS: The overall mortality was below expectation in the total cohort (SMR 0.92, 95% CI 0.90-0.94) and in each group of workers. The SMR of lung cancer was higher among bitumen workers (1.17, 95% CI 1.04-1.30) than among workers in ground and building construction (SMR 1.01, 95% CI 0.89-1.15). In the internal comparison, the relative risk (RR) of lung cancer mortality among bitumen workers was 1.09 (95% CI 0.89-1.34). The results of cancer of the head and neck were similar to those of lung cancer, based on a smaller number of deaths. There was no suggestion of an association between employment in bitumen jobs and other cancers. CONCLUSIONS: European workers employed in road paving, asphalt mixing and other jobs entailing exposure to bitumen fume might have experienced a small increase in lung cancer mortality risk, compared to workers in ground and building construction. However, exposure assessment was limited and confounding from exposure to carcinogens in other industries, tobacco smoking, and other lifestyle factors cannot be ruled out.

Adult↗

Cancer mortality among European asphalt workers: an international epidemiological study. II. Exposure to bitumen fume and other agents.

BACKGROUND: An increased risk of lung cancers among asphalt workers has been suggested in epidemiological studies based on large scale statistical analyses. METHODS: In a multi-country study of 29,820 male workers employed in road paving, asphalt mixing and roofing, 32,245 ground and building construction workers and 17,757 other workers from Denmark, Finland, France, Germany, Israel, the Netherlands, Norway, and Sweden, with mortality that was documented from 1953-2000. Exposures to bitumen fume, coal tar, 4-6 ring polycyclic aromatic hydrocarbons, organic vapor, diesel exhaust, asbestos, and silica dust were assessed via a job-exposure matrix. Standardized mortality ratios (SMRs) and 95% confidence intervals (CIs) based on national mortality rates, as well as relative risks (RRs) based on Poisson regression models were calculated. RESULTS: The SMR of lung cancer among workers exposed to bitumen fume (1.08, 95% CI 0.99-1.18) was comparable to that of non-exposed workers (SMR 1.05, 95% CI 0.92-1.19). In a sub-cohort of bitumen-exposed workers without exposure to coal tar, the SMR of lung cancer was 1.23 (95% CI 1.02-1.48). The analysis based on the semi-quantitative, matrix-based exposures in the whole cohort did not suggest an increased lung cancer risk following exposure to bitumen fume. However, in an analysis restricted to road pavers, based on quantitative estimate of bitumen fume exposure, a dose-response was suggested for average level of exposure, applying a 15-year lag, which was marginally reduced after adjustment for co-exposure to coal tar. The results for cancer of the head and neck were similar to those of lung cancer, although they were based on a smaller number of deaths. There was no clear suggestion of an association with bitumen fume for any other neoplasm. CONCLUSIONS: The results of the analysis by bitumen fume exposure do not allow us to conclude on the presence or absence of a causal link between exposure to bitumen fume and risk of cancer of the lung and the head and neck.

Adult↗

Estimating exposures in the asphalt industry for an international epidemiological cohort study of cancer risk.

BACKGROUND: An exposure matrix (EM) for known and suspected carcinogens was required for a multicenter international cohort study of cancer risk and bitumen among asphalt workers. METHODS: Production characteristics in companies enrolled in the study were ascertained through use of a company questionnaire (CQ). Exposures to coal tar, bitumen fume, organic vapor, polycyclic aromatic hydrocarbons, diesel fume, silica, and asbestos were assessed semi-quantitatively using information from CQs, expert judgment, and statistical models. Exposures of road paving workers to bitumen fume, organic vapor, and benzo(a)pyrene were estimated quantitatively by applying regression models, based on monitoring data, to exposure scenarios identified by the CQs. RESULTS: Exposures estimates were derived for 217 companies enrolled in the cohort, plus the Swedish asphalt paving industry in general. Most companies were engaged in road paving and asphalt mixing, but some also participated in general construction and roofing. Coal tar use was most common in Denmark and The Netherlands, but the practice is now obsolete. Quantitative estimates of exposure to bitumen fume, organic vapor, and benzo(a)pyrene for pavers, and semi-quantitative estimates of exposure to these agents among all subjects were strongly correlated. Semi-quantitative estimates of exposure to bitumen fume and coal tar exposures were only moderately correlated. EM assessed non-monotonic historical decrease in exposures to all agents assessed except silica and diesel exhaust. CONCLUSIONS: We produced a data-driven EM using methodology that can be adapted for other multicenter studies.

Cohort Studies↗

Lung function decrease in relation to pneumoconiosis and exposure to quartz-containing dust in construction workers.

BACKGROUND: Prevalence of exposure related respiratory symptoms and decreases in lung function are unknown among quartz dust exposed construction workers. METHODS: In a cross-sectional study (n = 1335), the occurrence of respiratory symptoms, was recorded and spirometric lung function was measured. Results were associated with exposure data and presence of radiographic abnormalities and compared with a reference population. RESULTS: Pneumoconiosis (profusion category 1/1 or greater) was associated with increased risks of FEV(1) and FVC values in the lowest 5% group, and with group-based decreases of 270 ml/s and 180 ml, respectively. Average lung function of construction workers was somewhat lower compared to a Dutch reference population. Lung function was not associated with exposure, except for a reduction in FVC of 5 ml per year for those with higher exposure. CONCLUSIONS: In quartz dust exposed construction workers obstructive and restrictive lung function loss was detected.

Adult↗

Neurological symptoms among Sri Lankan farmers occupationally exposed to acetylcholinesterase-inhibiting insecticides.

BACKGROUND: In many agricultural districts in Sri Lanka, pesticide poisoning is a leading cause of death. This study aims to evaluate the impact of pesticide use on Sri Lankan farmers' health. METHODS: A total of 260 subjects were surveyed in both a low and a high exposure period. Acetylcholinesterase activity was measured and data on symptoms were collected with questionnaires. RESULTS: Twenty-four percent of surveyed farmers had suffered at least once from acute pesticide poisoning. Farmers showed significantly more inhibition of cholinesterase activity than controls. Acute symptoms indicative for exposure to cholinesterase-inhibiting pesticides were associated with farming and a higher degree of cholinesterase suppression (more than 13% inhibition). Integrated Pest Management (IPM) training seemed to result in less insecticide use, and less cholinesterase inhibition. CONCLUSIONS: Our results suggest that occupational acetylcholinesterase-inhibiting insecticide exposures have a negative impact on Sri Lankan farmers' health. Overall reduction in pesticide use seems the best option to protect farmers from the adverse effects of pesticides.

Acetylcholinesterase↗

DREAM: a method for semi-quantitative dermal exposure assessment.

This paper describes a new method (DREAM) for structured, semi-quantitative dermal exposure assessment for chemical or biological agents that can be used in occupational hygiene or epidemiology. It is anticipated that DREAM could serve as an initial assessment of dermal exposure, amongst others, resulting in a ranking of tasks and subsequently jobs. DREAM consists of an inventory and evaluation part. Two examples of dermal exposure of workers of a car-construction company show that DREAM characterizes tasks and gives insight into exposure mechanisms, forming a basis for systematic exposure reduction. DREAM supplies estimates for exposure levels on the outside clothing layer as well as on skin, and provides insight into the distribution of dermal exposure over the body. Together with the ranking of tasks and people, this provides information for measurement strategies and helps to determine who, where and what to measure. In addition to dermal exposure assessment, the systematic description of dermal exposure pathways helps to prioritize and determine most adequate measurement strategies and methods. DREAM could be a promising approach for structured, semi-quantitative, dermal exposure assessment.

Environmental Exposure↗

Dust control measures in the construction industry.

Quartz is a human carcinogen and a causative agent of silicosis. Exposure levels often exceed exposure limits in the construction industry. The need for effective control measures is high, but the complex structure of the construction industry, the variability in sources of exposure and the frequent changes of worksite makes it difficult to implement even simple and potentially effective control measures. The aim of this study was to evaluate the impact of control measures for reducing quartz dust exposure and to assess the extent of their use. Full-shift respirable dust measurements (n = 61) and short-term measurements among construction workers were performed and results of a questionnaire study among 1335 construction workers were analysed. Full-shift measurements showed respirable quartz exposure levels up to 63 times the maximum allowable concentration (MAC) value (0.075 mg/m(3)). More than half of the measurements were above the MAC value. Control measures were not very strongly associated with the full-shift exposure estimates, but the short-term measurements showed large reduction factors (>70%) when wet dust suppression or local exhaust ventilation was used. The effectiveness of control measures is potentially high, and a significant part of the construction worker population is indeed using them on a regular basis. Still, both the exposure study and questionnaire survey show that the use of respiratory protection is the most widely used preventive measure in the construction industry. Respiratory protection might not always reduce exposure sufficiently. Only the combined use of more than one control measure can reduce exposures to acceptable levels.

Adult↗

Respiratory symptoms and occupation: a cross-sectional study of the general population.

BACKGROUND: This study focused on respiratory symptoms due to occupational exposures in a contemporary general population cohort. Subjects were from the Dutch Monitoring Project on Risk Factors for Chronic Diseases (MORGEN). The composition of this population enabled estimation of respiratory risks due to occupation from the recent past for both men and women. METHODS: The study subjects (aged 20-59) were all inhabitants of Doetinchem, a small industrial town, and came from a survey of a random sample of 1104 persons conducted in 1993. A total of 274 cases with respiratory symptoms (subdivided in asthma and bronchitis symptoms) and 274 controls without symptoms were matched for age and sex. Relations between industry and occupation and respiratory symptoms were explored and adjusted for smoking habits and social economic status. RESULTS: Employment in the 'construction' (OR = 3.38; 95%CI 1.02 - 11.27), 'metal' (OR = 3.17; 95%CI 0. 98 - 10.28), 'rubber, plastics and synthetics' (OR = 6.52; 95%CI 1.26 - 53.80), and 'printing' industry (OR = 3.96; 95%CI 0.85 - 18.48) were positively associated with chronic bronchitis symptoms. In addition, the 'metal' industry was found to be weakly associated with asthma symptoms (OR = 2.59; 95%CI 0.87 - 7.69). Duration of employment within these industries was also positively associated with respiratory symptoms. CONCLUSION: Respiratory symptoms in the general population are traceable to employment in particular industries even in a contemporary cohort with relatively young individuals.

Adult↗

Sources of bias in studies among infertility clients.

An assumption in case-control studies is that forces of selection are the same for cases and controls. This may not be true for studies of male infertility among infertility clients. Earlier reproductive outcomes may introduce modification of risk behavior or differential referral. Selection bias might also occur when infertile males are compared with fertile males. Partners of sterile men are more likely to have "normal" fertility, while partners of a reference group of normozoospermic men tend to have a lower fertility potential. The latter may lead to overrepresentation of causes of reduced female fertility and introduce bias into estimates of risk factors shared by couples. The relation between cigarette smoking and semen quality was studied in a population of infertility clients from the Netherlands during 1995-1996. To reduce the potential for bias, this relation was studied first in a restricted population less aware of the type of infertility involved. The odds ratio of infertility with smoking was elevated in the restricted population as compared with the total population. Adjustment for smoking by the female partner increased the odds ratios for male smoking as well. These results indicate that bias may occur in clinic-based fertility studies because of different forms of selection.

Adult↗

Bronchial responsiveness to adenosine 5'-monophosphate (AMP) and methacholine differ in their relationship with airway allergy and baseline FEV(1).

Bronchial hyperresponsiveness (BHR) and inflammation are central hallmarks of asthma. Studies in patients with asthma suggest that BHR to adenosine 5'-monophosphate (AMP) is a better marker of bronchial inflammation than BHR to methacholine. The association between markers of airway inflammation and BHR to methacholine and AMP in a population of young adults, with mild symptoms if any, was evaluated. A total of 230 subjects who participated in a follow-up study on occupational allergy were included. Before exposure to occupational allergens, subjects completed a questionnaire on respiratory symptoms and were tested for atopy, blood eosinophilia (> or =275/mm(3)), and BHR to methacholine and AMP (> or =15% fall in FEV(1)). Risk estimates were expressed as prevalence ratios (PR) and 95% confidence intervals (95% CI). Dose-response slopes (DRS) for methacholine and AMP were compared between healthy control subjects, self-reported allergic rhinitis, and allergic asthma. BHR to AMP was associated with allergic rhinitis (PR 2.51, 95% CI: 1.22;5.17), allergic asthma (PR 4.38, 95% CI: 1.98;9.66), with atopy (PR 3.87, 95% CI: 1.76;8.52), and blood eosinophilia (PR 3.57, 95% CI: 1.48;8.77), but not with baseline FEV(1). BHR to methacholine was inversely related to prechallenge FEV(1) (PR 0.97, 95% CI: 0.96;0.99). For both methacholine and AMP the geometric mean DRS increased along the axis asymptomatic-allergic rhinitis-allergic asthma, but for AMP the increase was the strongest. In this population study among young adults, BHR to AMP refers to allergic background of airway lability and BHR to methacholine is related to a diminished airway caliber.

Adenosine Monophosphate↗

Respiratory symptoms and dust exposure among male workers in small-scale wood industries in Tanzania.

Few studies have assessed respiratory symptoms and dust exposure levels in small-scale wood industry workers in Africa. We interviewed 546 workers exposed to wood dust and 565 control subjects using a respiratory health questionnaire. Inhalable dust measurements were collected for 106 workers. The dust exposure was high, and job title-based geometric mean exposure levels ranged from 2.9 to 22.8 mg/m3. Prevalence of respiratory symptoms in the previous 12 months was significantly higher in the exposed group compared with the nonexposed office workers. Allergy and sensitivity symptoms were reported regularly in the exposed group with Odds ratios and 95% confidence intervals (CIs) varying from 2.4 (95% CI = 1.8-3.1) for low- and 2.7 (1.8-4.0) for high-exposure groups compared with controls. We conclude that working in the small-scale wood industry in Tanzania is associated with an increased prevalence of respiratory symptoms.

Adult↗

Inter- and intraindividual variation of endotoxin- and beta(1 --> 3)-glucan-induced cytokine responses in a whole blood assay.

Inflammatory airway responses to bioaerosols and to their active compounds, such as endotoxin and beta(1 --> 3)-glucan, vary between individuals. These differences may be explained by variation in cytokine responsiveness, which can be assessed by in vitro stimulation tests with isolated blood leukocytes or lung macrophages. In large-scale population studies, ex vivo induced cytokine production may also be tested with a more simple 'whole blood assay' (WBA). However, applicability of a WBA to characterize a subject's responsiveness depends largely on its reproducibility. This study was conducted to: 1) assess the within- and between-subject variability in cytokine production in a WBA after stimulation with endotoxin or beta(1 --> 3)-glucan; and 2) to determine under which conditions this test is most discriminating between subjects and most reproducible within subjects. Blood was collected from 14 healthy volunteers, of whom 10 also participated on a second occasion. Each blood sample was used in two WBA tests; the first WBA was initiated two hours and the second 26 hours after venapuncture. The WBA test itself comprised overnight incubation with serial dilutions of endotoxin [lipopolysaccharide (LPS)] and curdlan (a beta(1 --> 3)-glucan), after which blood cell supernatant was collected. Interleukin(IL)-1beta, IL6, IL8 and tumor necrosis factor alpha (TNFalpha) were determined in the supernatant. In all individuals, a dose-dependent production of cytokines was observed for both LPS and curdlan. For all cytokines, variation between subjects was higher than within subjects, and this was most pronounced for IL1beta and IL6. There was moderate-to-high correlation in the induced release of all four cytokines, and between cytokine release induced by LPS or curdlan. Optimal stimulation concentrations were 6.25 and 12.5 ng/mL for endotoxin and 12500 and 25000 ng/mL for curdlan. Cytokine production in WBA initiated 26 hours after venapuncture showed lower between-subject and larger within-subject variance, thus favoring an early initiation of the assay. In conclusion, measuring endotoxin- or glucan-induced cytokine production in a WBA initiated within two hours after venapuncture appears to be an effective method to determine a person's cytokine responsiveness, at least in healthy naive subjects.

Adult↗

Health-based occupational exposure limits for high molecular weight sensitizers: how long is the road we must travel?

In this paper pitfalls in risk assessment for high molecular weight allergens, which can cause typical Type I/IgE-mediated respiratory allergy, are discussed. The major pitfalls seem to be that no agreement exists on the preferential end point that should be used in risk assessment. As a result, it is unclear which exposure-response relationship should be considered. In addition, there is a lack of data on health risks for non-occupationally exposed reference populations, so the baseline risk is often not known and little is known about the shape of exposure-response relationships and the existence of exposure thresholds. The good news is that more and more groups have published exposure-response relationships for several allergens. The possibilities for risk assessment approaches that should lead to occupational exposure standards are explored. Specific consideration is given to situations in which data on exposure-response relationships for humans are available. Considerable progress has been made in this area by use of advanced statistical techniques for exposure-response modelling. The major practical constraint at this moment seems to be the absence of well-standardized measurement techniques (immunoassays) for the evaluation of allergen exposure in the field.

Allergens↗

Characterizing worker exposure to bitumen during hot mix paving and asphalt mixing operations.

A survey of bitumen exposure was carried out during hot mix paving and asphalt mixing. Four methods of characterizing and quantifying bitumen fume in inhalable particles were used: gravimetric, infrared spectroscopy, gas chromatography, and total absorbance (of the particle filter surface). Dermal deposition of bitumen was assessed by determination of cyclohexanesoluble matter in the material collected by paper or cotton pads worn on the inside of a person's wrists. The researchers studied the correlation patterns between results of these methods using pairwise correlation coefficients and principal component analysis (for air concentrations only). For hot mix paving, within- and between-worker variance components were evaluated, adjusting for area paved. Collected fume was dark in color and mainly consisted of aliphatic hydrocarbons of less than 20 carbon atoms. Inconsistent correlation patterns between dermal deposition and air levels were observed. Quantification of organic matter using either infrared spectroscopy or gas chromatography appeared to be good methods for monitoring inhalable bitumen fume. Cotton pads seem to be more promising than paper pads for measuring dermal exposure during paving. Paving workers were uniformly exposed to bitumen fume. Assessment of the uniformity of dermal exposure depended on the type of pad used. Day-to-day variability and intensity of inhalable and dermal bitumen exposures depended on area paved. The small size of the study limits the potential application of the results to the asphalt industry in general. More research is needed to develop a valid and inexpensive method of assessing total bitumen exposure.

Cotton Fiber↗