Manolis Kogevinas

Exposure to substances in the workplace and new-onset asthma: an international prospective population-based study (ECRHS-II)

BACKGROUND The role of exposure to substances in the workplace in new-onset asthma is not well characterised in population-based studies. We therefore aimed to estimate the relative and attributable risks of new-onset asthma in relation to occupations, work-related exposures, and inhalation accidents. METHODS We studied prospectively 6837 participants from 13 countries who previously took part in the European Community Respiratory Health Survey (1990-95) and did not report respiratory symptoms or a history of asthma at the time of the first study. Asthma was assessed by methacholine challenge test and by questionnaire data on asthma symptoms. Exposures were defined by high-risk occupations, an asthma-specific job exposure matrix with additional expert judgment, and through self-report of acute inhalation events. Relative risks for new onset asthma were calculated with log-binomial models adjusted for age, sex, smoking, and study centre. FINDINGS A significant excess asthma risk was seen after exposure to substances known to cause occupational asthma (Relative risk=1.6, 95% CI 1.1-2.3, p=0.017). Risks were highest for asthma defined by bronchial hyper-reactivity in addition to symptoms (2.4, 1.3-4.6, p=0.008). Of common occupations, a significant excess risk of asthma was seen for nursing (2.2, 1.3-4.0, p=0.007). Asthma risk was also increased in participants who reported an acute symptomatic inhalation event such as fire, mixing cleaning products, or chemical spills (RR=3.3, 95% CI 1.0-11.1, p=0.051). The population-attributable risk for adult asthma due to occupational exposures ranged from 10% to 25%, equivalent to an incidence of new-onset occupational asthma of 250-300 cases per million people per year. INTERPRETATION Occupational exposures account for a substantial proportion of adult asthma incidence. The increased risk of asthma after inhalation accidents suggests that workers who have such accidents should be monitored closely.

Occupational exposure to carcinogens in the European Union

OBJECTIVES To construct a computer assisted information system for the estimation of the numbers of workers exposed to established and suspected human carcinogens in the member states of the European Union (EU). METHODS A database called CAREX (carcinogen exposure) was designed to provide selected exposure data and documented estimates of the number of workers exposed to carcinogens by country, carcinogen, and industry. CAREX includes data on agents evaluated by the International Agency for Research on Cancer (IARC) (all agents in groups 1 and 2A as of February 1995, and selected agents in group 2B) and on ionising radiation, displayed across the 55 industrial classes. The 1990–3 occupational exposure was estimated in two phases. Firstly, estimates were generated by the CAREX system on the basis of national labour force data and exposure prevalence estimates from two reference countries (Finland and the United States) which had the most comprehensive data available on exposures to these agents. For selected countries, these estimates were then refined by national experts in view of the perceived exposure patterns in their own countries compared with those of the reference countries. RESULTS About 32 million workers (23% of those employed) in the EU were exposed to agents covered by CAREX. At least 22 million workers were exposed to IARC group 1 carcinogens. The exposed workers had altogether 42 million exposures (1.3 mean exposures for each exposed worker). The most common exposures were solar radiation (9.1 million workers exposed at least 75% of working time), environmental tobacco smoke (7.5 million workers exposed at least 75% of working time), crystalline silica (3.2 million exposed), diesel exhaust (3.0 million), radon (2.7 million), and wood dust (2.6 million). CONCLUSION These preliminary estimates indicate that in the early 1990s, a substantial proportion of workers in the EU were exposed to carcinogens.

Geographical variation in the prevalence of positive skin tests to environmental aeroallergens in the European Community Respiratory Health Survey I

Background:  Many studies have reported the prevalence of sensitization using skin prick tests. However, comparisons between studies and between regions are difficult because the number and the type of allergens tested vary widely. Using the European Community Health Respiratory Survey I data, the geographical variation of sensitization to environmental allergen as measured by skin tests was established.

Genomic DNA hypomethylation as a biomarker for bladder cancer susceptibility in the Spanish Bladder Cancer Study: a case-control study.

BACKGROUND DNA hypomethylation has been suggested to cause genomic instability and increase cancer risk. We aimed to test the hypothesis that DNA hypomethylation is associated with increased risk of bladder cancer. METHODS We measured cytosine methylation (5-mC) content in genomic DNA from blood cells from patients with bladder cancer enrolled in a large case-control study in Spain between Jan 1, 1998, and Dec 31, 2001. Cases were men and women with newly diagnosed and histologically confirmed urothelial carcinoma of the bladder. Controls were selected from patients admitted to the same hospital for diseases or conditions unrelated to smoking or other known risk factors for bladder cancer. Controls were individually matched to cases on age (within 5 years), sex, race, and area of hospital referral. 5-mC content was measured in leucocyte DNA by use of a combination of high-performance capillary electrophoresis, Hpa II digestion, and densitometry. Data on demographics, 34 polymorphisms in nine folate metabolism genes, and nutritional intake of six B vitamins (including folate), alcohol, and smoking were assessed as potential confounders. Relative 5-mC content was expressed as a percentage (%5-mC) with respect to the total cytosine content (the sum of methylated and non-methylated cytosines). The primary endpoint was median %5-mC DNA content. FINDINGS %5-mC was measured in leucocyte DNA from 775 cases and 397 controls. Median %5-mC DNA was significantly lower in cases (3.03% [IQR 2.17-3.56]) than in controls (3.19% [2.46-3.68], p=0.0002). All participants were subsequently categorised into quartiles by %5-mC content in controls. When the highest quartile of %5-mC content was used as the reference category (Q4), the following adjusted odds ratios (OR) and 95% CI were recorded for decreasing methylation quartiles: OR(Q3) 2.05 (95% CI 1.37-3.06); OR(Q2) 1.62 (1.07-2.44); and OR(Q1) 2.67 (1.77-4.03), p for trend <0.0001. The lowest cancer risk was noted in never smokers in the highest methylation quartile (never smokers in Q4). By comparison with never smokers in the highest quartile, current smokers in the lowest methylation quartile had the highest risk of bladder cancer (Q1: OR 25.51 [9.61-67.76], p for interaction 0.06). In analyses stratified by smoking, hypomethylation was a strong risk factor in never smokers (OR 6.39 [2.37-17.22]). Amount of methylation in controls were not associated with baseline characteristics, micronutrients, or selected genotypes in folate metabolism pathways. INTERPRETATION For the first time, to our knowledge, we have shown in a large case-control study that leucocyte DNA hypomethylation is associated with increased risk of developing bladder cancer, and this association is independent of smoking and the other assessed risk factors. Amount of global methylation in genomic DNA could provide a useful biomarker of susceptibility to certain cancer types and further research is warranted.

What's in the pool? A comprehensive identification of disinfection by-products and assessment of mutagenicity of chlorinated and brominated swimming pool water

Background Swimming pool disinfectants and disinfection by-products (DBPs) have been linked to human health effects, including asthma and bladder cancer, but no studies have provided a comprehensive identification of DBPs in the water and related that to mutagenicity. Objectives We performed a comprehensive identification of DBPs and disinfectant species in waters from public swimming pools in Barcelona, Catalonia, Spain, that disinfect with either chlorine or bromine and we determined the mutagenicity of the waters to compare with the analytical results. Methods We used gas chromatography/mass spectrometry (GC/MS) to measure trihalomethanes in water, GC with electron capture detection for air, low- and high-resolution GC/MS to comprehensively identify DBPs, photometry to measure disinfectant species (free chlorine, monochloroamine, dichloramine, and trichloramine) in the waters, and an ion chromatography method to measure trichloramine in air. We assessed mutagenicity with the Salmonella mutagenicity assay. Results We identified > 100 DBPs, including many nitrogen-containing DBPs that were likely formed from nitrogen-containing precursors from human inputs, such as urine, sweat, and skin cells. Many DBPs were new and have not been reported previously in either swimming pool or drinking waters. Bromoform levels were greater in brominated than in chlorinated pool waters, but we also identified many brominated DBPs in the chlorinated waters. The pool waters were mutagenic at levels similar to that of drinking water (~ 1,200 revertants/L-equivalents in strain TA100–S9 mix). Conclusions This study identified many new DBPs not identified previously in swimming pool or drinking water and found that swimming pool waters are as mutagenic as typical drinking waters.

Asthma, chronic bronchitis, and exposure to irritant agents in occupational domestic cleaning: a nested case-control study

Background: Women employed in domestic cleaning are at increased risk for symptoms of obstructive lung disease, but the agents responsible are unknown. Aims: To investigate common tasks and products in occupational domestic cleaning in relation to respiratory morbidity. Methods: Case-control study in domestic cleaning women nested within a large population based survey of women aged 30–65 years; 160 domestic cleaning women with asthma symptoms, chronic bronchitis symptoms, or both and 386 without a history of respiratory symptoms were identified. Detailed exposures were evaluated for 40 cases who reported still having symptoms at the recruitment interview, and 155 controls who reported not having symptoms. All tasks performed and products used when cleaning houses were determined in a face-to-face interview. Lung function, methacholine challenge, and serum IgE testing were performed. Personal exposure measurements of airborne chlorine and ammonia were performed in a subsample. Associations between asthma, chronic bronchitis, and cleaning exposures were evaluated using multiple logistic regression analysis. Results: Airborne chlorine (median level 0–0.4 ppm) and ammonia (0.6–6.4 ppm) were detectable during occupational domestic cleaning activities. Cases used bleach more frequently than controls; adjusted odds ratio (OR) for intermediate exposure was 3.3 (95% CI 0.9 to 11) and for high exposure 4.9 (1.5 to 15). Other independent associations included accidental inhalation of vapours and gases from cleaning agents and washing dishes. These associations were more pronounced for cases with asthma symptoms than for those with symptoms of chronic bronchitis, but were not related to sensitisation to common allergens. Conclusions: Asthma symptoms in domestic cleaning women are associated with exposure to bleach and possibly other irritant agents. The public health impact of the use of irritant cleaning products could be widespread since the use of these products is common both in the workplace and at home.

Soft tissue sarcoma and non-Hodgkin's lymphoma in workers exposed to phenoxy herbicides, chlorophenols, and dioxins: two nested case-control studies

We examined the effect of exposure to chemicals present in the production and spraying of phenoxy herbicides or chloro-phenols in two nested case-control studies of soft tissue sarcoma and non-Hodgkins lymphoma. Eleven sarcoma and 32 lymphoma cases occurring within an international cohort were matched for age, sex, and country of residence with 55 and 158 controls, respectively. Exposures to 21 chemicals or mixtures were estimated by three industrial hygienists who were blind to the subjects case-control status. Excess risk of soft tissue sarcoma was associated with exposure to any phenoxy herbicide [odds ratio (OR) = 10.3; 95% confidence interval (Cl) = 1.2–91] and to each of the three major classes of phenoxy herbicides (2,4-dichlorophenoxyacetic acid, 2,4,5-trichloro-phenoxyacetic acid, and 4-chloro-2-methylphenoxyacetic acid), to any polychlorinated dibenzodioxin or furan (OR = 5.6; 95% CI = 1.1–28), and to 2,3,7,8-tetrachlorodibenzo-p-dioxm (OR = 5.2; 95% CI = 0.85–32). Sarcoma risk was not associated with exposure to raw materials or other process chemicals. In the non-Hodgkins lymphoma study, associations were generally weaker than those found in the study on sarcoma. These findings indicate that workers exposed to phenoxy herbicides and their contaminants are at a higher risk of soft tissue sarcoma.

Polychlorinated biphenyls (PCBs) and neurological development in children: a systematic review

BACKGROUND Polychlorinated biphenyls (PCBs) are complex mixtures of persistent contaminants that are widespread in the environment. Newborns are exposed across the placenta and through breast feeding. Experimental animal studies have indicated that PCBs are neurotoxic. The neurological effects of these compounds on children are not clear.Methods—A systematic review of literature on the relation between neurological development in children and exposure to polychlorinated biphenyls. RESULTS Seven follow up studies evaluated the effect of prenatal exposure to PCBs. Two of these studies evaluated highly exposed children. In newborns, an increase of the abnormal reflexes was observed in all four studies evaluating it. During the first months of life, a decrease in motor skills was observed in four of the five studies that investigated psychomotor development; deficits in the acquisition of cognitive skills were observed only in one study assessing non-highly exposed populations. At 4 years of age, an effect on the cognitive areas was observed in four of the five studies that evaluated it. Postnatal exposure to PCBs through breast feeding was not clearly related to any effect on neurological development. CONCLUSIONS These studies suggest a subtle adverse effect of prenatal PCBs exposure on child neurodevelopment. Differences in study design, inconsistency in some of the results, and the lack of adequate quantitative exposure data, do not allow the derivation of the degree of risk associated with neurodevelopmental effects at current levels of exposure.

Asthma symptoms in women employed in domestic cleaning: a community based study

Background: Epidemiological studies have shown an association between cleaning work and asthma, but the risk factors are uncertain. The aim of this study was to assess the risk of asthma in women employed in domestic cleaning. Methods: A cross sectional study was conducted in 4521 women aged 30 to 65 years. Information on respiratory symptoms and cleaning work history was obtained using a postal questionnaire with telephone follow up. Asthma was defined as reported symptoms in the last year or current use of drugs to treat asthma. Odds ratios (OR) with 95% confidence intervals (CI) for asthma in different cleaning groups were estimated using adjusted unconditional logistic regression models. Results: 593 women (13%) were currently employed in domestic cleaning work. Asthma was more prevalent in this group than in women who had never worked in cleaning (OR 1.46 (95% CI, 1.10 to 1.92)). Former domestic cleaning work was reported by 1170 women (26%), and was strongly associated with asthma (OR 2.09 (1.70 to 2.57)). Current and former non-domestic cleaning work was not significantly associated with asthma. Consistent results were obtained for other respiratory symptoms. Twenty five per cent of the asthma cases in the study population were attributable to domestic cleaning work. Conclusions: Employment in domestic cleaning may induce or aggravate asthma. This study suggests that domestic cleaning work has an important public health impact, probably involving not only professional cleaners but also people undertaking cleaning tasks at home.

Biomarkers of exposure to polycyclic aromatic hydrocarbons from environmental air pollution

Metabolites of pyrene and DNA adducts have been used as biomarkers of high level exposure to polycyclic aromatic hydrocarbons (PAHs). A systematic review was performed to evaluate whether these biomarkers are also valid markers of low level environmental exposure to PAHs. Thirty five studies were identified with more than 10 subjects that evaluated environmental air pollution to PAHs in relation to metabolites of PAHs, mainly hydroxypyrene (1-OHP), PAH-DNA adducts, or protein adducts. PAH metabolites and, to a less extent, PAH-DNA adducts correlated well at the group level with exposure to B(a)P even at low levels of air pollution. The use of these biomarkers should be more widely implemented in combination with more traditional techniques for the assessment of general population exposure to PAHs from ambient air pollution.