Exposure to grass pollen--but not birch pollen--affects lung function in Swedish children.

Allergic response to pollen is increasing worldwide, leading to high medical and social costs. However, the effect of pollen exposure on lung function has rarely been investigated. Over 1800 children in the Swedish birth cohort BAMSE were lung-function- and IgE-tested at the age of 8 and 16 years old. Daily concentrations for 9 pollen types together with measurements for ozone, NO2 , PM10 , PM2.5 were estimated for the index day as well as up to 6 days before the testing. Exposure to grass pollen during the preceding day was associated with a reduced forced expiratory volume in 8-yr-olds; -32.4 ml; 95% CI: -50.6 to -14.2, for an increase in three pollen counts/m³. Associations appeared stronger in children sensitized to pollen allergens. As the grass species flower late in the pollen season, the allergy care routines might be weakened during this period. Therefore, allergy information may need to be updated to increase awareness among grass pollen-sensitized individuals.

Interaction between smoking and the interleukin-6 gene affects systemic levels of inflammatory biomarkers.

BACKGROUND: Smoking is associated with a systemic inflammatory response. However, the role of genetic predisposition is not well known. We assessed whether circulatory acute phase reactants were associated with smoking and whether or not the association was modified by the major cytokine gene of the acute phase reaction, interleukin-6 (IL-6). METHODS: In total, 1,003 postmyocardial infarction patients were recruited in six European cities and six repeated clinical examinations performed. C-reactive protein (CRP), interleukin 6 (IL-6), and fibrinogen levels were assayed at 5,659 subject visits. Genotyping of single nucleotide polymorphisms was performed in the IL-6 gene. RESULTS: Cumulative smoking (pack-years) and time since smoking cessation were strongly associated with blood levels of all three inflammatory markers. Among subjects without any respiratory disorder, these associations remained statistically significant for CRP and IL-6. A polymorphism in the IL-6 gene (rs2069840) showed an interaction with smoking on CRP (p < .001) and IL-6 (p = .049) peripheral levels. CONCLUSIONS: These results indicate a potential role of the IL-6 gene in the inflammatory response associated with smoking and suggest rs2069840 polymorphism deserves attention.

Associations of long- and short-term air pollution exposure with markers of inflammation and coagulation in a population sample.

BACKGROUND: Exposure to elevated levels of ambient air pollutants can lead to adverse cardiovascular effects. Potential mechanisms include systemic inflammation and perturbation of the coagulation balance. OBJECTIVES: To investigate long- and short-term effects of air pollution exposure on serum levels of inflammatory (IL-6, TNF-alpha and CRP) and coagulation (fibrinogen and PAI-1) markers relevant for cardiovascular pathology. METHODS: The study group consisted of a population sample of 1028 men and 508 women aged 45-70 years from Stockholm. Long-term air pollution exposure was assessed using spatial modelling of traffic-related NO(2) and heating-related SO(2) emissions at each subject's residential addresses over retrospective periods of 1, 5 and 30 years. Short-term exposure was assessed as averages of rooftop measurements over 12-120 h before blood sampling. RESULTS: Long-term exposures to both traffic-NO(2) and heating-SO(2) emissions showed consistent associations with IL-6 levels. 30-year average traffic-NO(2) exposure was associated with a 64.5% (95% CI 6.7% to 153.8%) increase in serum IL-6 per 28.8 microg/m(3) (corresponding to the difference between the 5th and 95th percentile exposure value), and 30-year exposure to heating-SO(2) with a 67.6% (95% CI 7.1% to 162.2%) increase per 39.4 microg/m(3) (5th-95th percentile value difference). The association appeared stronger in non-smokers, physically active people and hypertensive subjects. We observed positive non-significant associations of inflammatory markers with NO(2) and PM(10) during 24 h before blood sampling. Short-term exposure to O(3) was associated with increased, and SO(2) with decreased, fibrinogen levels. CONCLUSIONS: Our results suggest that exposure to moderate levels of air pollution may influence serum levels of inflammatory markers.

Urban residential greenness and adiposity: A cohort study in Stockholm County.

BACKGROUND: Increasing evidence suggests that exposure to residential greenness is associated with positive health outcomes among urban populations. However, few studies have considered effects on adiposity development in a longitudinal setting. OBJECTIVES: This study aimed to explore the association between long-term exposure to urban residential greenness and markers of adiposity. METHODS: A cohort of 5126 adults from five municipalities in Stockholm County was examined clinically at baseline (1992-1998) and follow-up (2002-2006) after on average nine years. Time-weighted average exposure to urban greenness was estimated by Normalized Difference Vegetation Index (NDVI) within 100 m, 250 m, and 500 m buffers around the residential addresses of each participant. Multiple linear and Poisson regression models were used to estimate associations between greenness and change in weight and waist circumference as well as risk of overweight, obesity and central obesity. Co-exposures to air pollution, traffic noise and distance to water were also examined. RESULTS: In women, higher levels of residential greenness were associated with a reduced increase in waist circumference during follow-up (ß = -0.11 cm/year, 95% CI -0.14; -0.08 per one interquartile range increase in NDVI) and decreased risk for central obesity (IRR = 0.88: 95% CI 0.79; 0.99) in the 500 m buffer. No associations were observed for men or with regard to weight development or the risk of developing overweight or obesity. Exposure to low NDVI levels in combination with high NOx from road traffic and transportation noise as well as long distance to water rendered statistically significant increases in waist circumference in both sexes. CONCLUSION: Higher long-term exposure to greenness was associated with a reduced increase in waist circumference and lower risk of central adiposity in women but not in men. In both sexes, low NDVI exposure in combination with other environmental risk factors appeared particularly harmful.

Comparison of parental reports of smoking and residential air nicotine concentrations in children.

BACKGROUND: Using questionnaires to assess children's residential exposure to environmental tobacco smoke (ETS) may result in misclassification from recall and response bias. Questionnaire data have frequently been validated against urinary cotinine measurements, but rarely against actual measurements of residential air nicotine. OBJECTIVE: To compare questionnaire reported smoking with air nicotine concentrations in a large population of children and with urinary cotinine levels in a subpopulation; and to assess the potential impact of the symptom status of the children on the agreement between different measures of exposure. METHODS: The authors assessed residential exposure to ETS in 347 German, 335 Dutch, and 354 Swedish preschool and schoolchildren by questionnaire and air nicotine measurements, and in a subset of 307 German children by urinary cotinine measurements. They then compared the different measures of ETS exposure. RESULTS: In all countries, air nicotine concentrations increased with increasing questionnaire reported smoking in a dose-response fashion. Specificity and negative predictive values of questionnaire reports for nicotine concentrations were excellent. Sensitivity and positive predictive values were moderate to good. Excluding occasional smokers, the overall percentage of homes misclassified was 6.9%, 6.7%, and 5.1% in Germany, the Netherlands, and Sweden, respectively. Similar results were found for the agreement of urinary cotinine concentrations with questionnaire reports and air nicotine levels. There was no indication of underreporting by parents of symptomatic children. CONCLUSION: Despite some misclassification, questionnaire reports are an inexpensive and valid estimate of residential ETS exposure among preschool and school children.

Exposure to traffic related air pollutants: self reported traffic intensity versus GIS modelled exposure.

BACKGROUND: In epidemiological studies of the potential health effects of traffic related air pollution, self reported traffic intensity is a commonly used, but rarely validated, exposure variable. METHODS: As part of a study on the impact of Traffic Related Air Pollution on Childhood Asthma (TRAPCA), data from 2633 and 673 infants from the Dutch and the German-Munich cohorts, respectively, were available. Parents subjectively assessed traffic intensity at the home address. Objective exposures were estimated by a combination of spatial air pollution measurements and geographic information system (GIS) based modelling using an identical method for both cohorts. RESULTS: The agreement rates between self reported and GIS modelled exposure--accumulated over the three strata of self assessed traffic intensity--were 55-58% for PM(2.5), filter absorbance (PM(2.5) abs), and nitrogen dioxide in Munich and 39-40% in the Netherlands. Of the self reported low traffic exposed group, 71-73% in Munich and 45-47% in the Netherlands had low modelled exposure to these three air pollutants. Of the self assessed high exposed subgroups in Munich (15% of the total population) and the Netherlands (22% of the total population), only 22-33% and 30-32% respectively had high modelled exposure to the three air pollutants. The subjective assessments tend to overestimate the modelled estimates for PM(2.5) and NO2 in both study areas. When analysis was restricted to the portion of the Dutch cohort living in non-urban areas, the agreement rates were even lower. CONCLUSIONS: Self reported and modelled assessment of exposure to air pollutants are only weakly associated.

Using geographic information systems to assess individual historical exposure to air pollution from traffic and house heating in Stockholm.

A specific aim of a population-based case-control study of lung cancer in Stockholm, Sweden, was to use emission data, dispersion models, and geographic information systems (GIS) to assess historical exposure to several components of ambient air pollution. Data collected for 1,042 lung cancer cases and 2,364 population controls included information on residence from 1955 to the end of follow-up for each individual, 1990-1995. We assessed ambient air concentrations of pollutants from road traffic and heating throughout the study area for three points in time (1960, 1970, and 1980) using reconstructed emission data for the index pollutants nitrogen oxides (NO(x)/NO(2)) and sulfur dioxide together with dispersion modeling. NO(2) estimates for 1980 compared well with actual measurements, but no independently measured (study-external) data were available for SO(2), precluding similar validation. Subsequently, we used linear intra- and extrapolation to obtain estimates for all other years 1955-1990. Eleven thousand individual addresses were transformed into geographic coordinates through automatic and manual procedures, with an estimated error of < 100 m for 90% of the addresses. Finally, we linked annual air pollution estimates to annual residence coordinates, yielding long-term residential exposure indices for each individual. There was a wide range of individual long-term average exposure, with an 11-fold interindividual difference in NO(2) and an 18-fold difference in SO(2). The 30-year average for all study subjects was 20 microg/m(3) NO(2) from traffic and 53 microg/m(3) SO(2) from heating. The results indicate that GIS can be useful for exposure assessment in environmental epidemiology studies, provided that detailed geographically related exposure data are available for relevant time periods.

Mortality and cancer morbidity among workers in a chemical factory.

A retrospective cohort study was performed on a group of 664 male workers employed for at least one month during the period 1942-1979 in a chemical factory. Both established and suspected carcinogens had been handled in the plant, primarily piperazine, but also urethane, ethylene oxide, formaldehyde, and organic solvents. A significantly increased mortality, compared with the regional death rate, was observed in the cohort. The increase was mainly due to violent deaths and cardiovascular diseases. No rise in death rates was observed for asthma, bronchitis or emphysema, in spite of other evidence of a high risk of occupational asthma, due to exposure to piperazine. A statistically significant increase in cancer morbidity was observed for malignant lymphoma/myelomatosis when an induction latency time of at least 10 years was used. Furthermore, an increase in bronchial cancer was noted, but it was statistically significant only when an induction-latency time of at least 15 years was used. A case-referent study within the cohort did not reveal any significant association between any specific chemical exposure and cancer morbidity.

Cancer mortality in a historical cohort study of workers exposed to styrene.

OBJECTIVES: The goal of this study was to determine whether exposure to styrene is associated with an increased risk for neoplasms of the lymphatic and hematopoietic tissues. METHODS: A historical cohort study was conducted in Denmark, Finland, Italy, Norway, Sweden, and the United Kingdom. It involved 40,688 workers ever employed in the reinforced plastics industry, where high exposure to styrene occurs. Exposure to styrene was reconstructed through job histories and environmental and biological monitoring data. Cause-specific national death rates were used as the reference. Poisson regression was applied for internal comparisons. RESULTS: Among the exposed workers, no excess was observed for mortality from all neoplasms. Mortality from neoplasms of the lymphatic and hematopoietic tissues increased with time since first exposure and average level of exposure to styrene, but was not consistently associated with duration of exposure or with cumulative exposure. CONCLUSIONS: These findings leave open the possibility of an excess risk of neoplasms of the lymphatic and hematopoietic tissues among workers exposed to styrene.

Exposure to styrene and mortality from nonmalignant diseases of the genitourinary system.

OBJECTIVES: A historical cohort study was carried out to investigate mortality from nonmalignant diseases of the genitourinary system among workers in the reinforced plastics industry, where high workroom concentrations of styrene are encountered. METHODS: The external comparisons in this report were based on an average of 12.6 years of retrospective follow-up of 35 443 workers who were first employed in the reinforced plastics industry during 1945-1991 and were known to have been exposed to styrene in their work. For the internal comparisons, 2641 subjects with incomplete occupational histories were excluded, leaving 32 802 subjects. Previous individual exposure histories to styrene were reconstructed through job histories and environmental and biological monitoring data. RESULTS: Mortality from nonmalignant diseases of the genitourinary system (N = 20) was associated with average exposure to styrene (P for trend 0.05). Weaker increasing trends in risk were seen for time since first exposure and cumulative exposure, while no increase was identified for duration of exposure. There was a significant increasing trend in mortality from nephritis and nephrosis (N = 5), associated with an increasing average level of exposure to styrene (P for trend 0.03). No clear trend was observed for time since first exposure, duration of exposure, or cumulative exposure. CONCLUSIONS: In this large cohort study of workers exposed to styrene, mortality from nonmalignant diseases of the genitourinary system increased as the average intensity of exposure increased. This finding indicates that other data should be scrutinized.

Acute myeloid leukemia among petrol station attendants.

The risk of acute myeloid leukemia (AML) within different occupations was studied, using occupational information obtained from the Swedish 1970 census. Follow-up in the Swedish Cancer Register was carried out from 1971 to 1984. Among male petrol station attendants, 10 cases were observed versus 2.8 expected (observed/expected = 3.6, 95% confidence interval 1.7-6.6). For several decades, Swedish petrol has contained 3-5% of benzene. Thus, a hypothesis was that benzene had contributed to the excess risk. The work histories of the 10 cases were reconstructed through interviews with surviving relatives and were compatible with the hypothesis. However, because the air benzene exposures at petrol stations always have been lower than benzene exposures associated previously with an increased risk of AML, the leukemogenic effect of benzene may have been potentiated by other petrol or vehicle exhaust components.

Determinants of house dust endotoxin in three European countries - the AIRALLERG study.

UNLABELLED: The comparison of endotoxin levels between study populations and countries is limited as a result of differences in sampling, extraction, and storage procedures. The objective of this study is to assess the levels and determinants of endotoxin in mattress and living room floor dust samples from three European countries, namely, Germany, the Netherlands, and Sweden, using a standardized sampling, storage, and analysis protocol. The mattress and living room floor dust was collected from the homes of 1065 German, Dutch, and Swedish (pre-)school children. All the samples were collected in the cool season and analyzed for endotoxin in a central laboratory. The determinants were assessed by a standardized questionnaire. The endotoxin concentrations in mattress and living room floor dust were found to be the highest in German homes and lowest in the Swedish ones. Differences between the geometric means were small (factor 1.1-1.7). Most of the associations between endotoxin concentrations and potential determinants were not statistically significant and heterogeneous across countries. However, keeping pets and having more than four persons living in the home were consistently associated with up to 1.7-fold higher endotoxin concentrations in mattress and floor dust. Furthermore, having carpets or rugs, and opening the windows frequently was associated with up to 3.4-fold and 1.3-fold higher endotoxin concentrations in living room floor dust, respectively. The proportion of variance explained by the questionnaire variables was generally low. In conclusion, the data on housing characteristics did not accurately predict the endotoxin concentrations in house dust, and could only partly explain the differences between countries. PRACTICAL IMPLICATIONS: The differences between the endotoxin concentrations in German, Dutch, and Swedish homes are small. House dust endotoxin concentrations are associated with a number of housing factors, such as pet-ownership, floor cover, number of persons living in the home, and ventilation. The variability of the endotoxin levels between homes and countries can only be partly explained by these factors.

Bacteria and mould components in house dust and children's allergic sensitisation.

It has been suggested that early childhood exposure to microbial agents decreases the risk of allergies in children. The current authors studied the association between microbial agents in house dust and allergic sensitisation in children aged 2-4 yrs. Nested case-control studies were performed within ongoing birth cohort studies in Germany, the Netherlands and Sweden and approximately 180 sensitised and 180 nonsensitised children were selected per country. Levels of bacterial endotoxin, beta(1,3)-glucans and fungal extracellular polysaccharides (EPS) were measured in dust samples from the children's mattresses and the living-room floors. Combined across countries, higher amounts of mattress dust and higher mattress dust loads of endotoxin, beta(1,3)-glucans and EPS were associated with a significantly decreased risk of sensitisation to inhalant allergens. After mutual adjustment, only the protective effect of the amount of mattress dust remained significant (odds ratio (95% confidence interval) 0.57(0.39-0.84)). Higher amounts of mattress dust may decrease the risk of allergic sensitisation to inhalant allergens. The effect might be partly attributable to endotoxin, beta(1,3)-glucans and extracellular polysaccharides, but could also reflect (additional) protective effects of (microbial) agents other than the ones measured. It is not possible to distinguish with certainty which component relates to the effect, since their levels are highly correlated.

Determination of piperazine in working atmosphere and in human urine using derivatization and capillary gas chromatography with nitrogen- and mass-selective detection.

A reliable routine method is presented for the determination of piperazine down to the sub-ppm level in aqueous solutions and in urine. The method includes a two-phase derivatization procedure with ethyl- or isobutyl chloroformate as the reagent, followed by a capillary gas chromatographic determination using nitrogen- or mass selective detection. The addition of ammonia ensured a quantitative recovery. Detection limits for piperazine in urine were ca. 20 ng/ml using nitrogen-selective and ca. 1 ng/ml with mass-selective detection. The calibration plots were linear in the investigated range, 100-10,000 ng/ml with nitrogen-selective and 30-3000 ng/ml with mass-selective detection. The precision was ca. 6% at a concentration of 300 ng/ml. Acid anhydrides were investigated as alternative reagents in the two-phase derivatization procedure, and heptafluorobutyric acid anhydride in aqueous solutions gave approximately 100% recovery. However, in urine the recoveries of the investigated acid anhydride derivatives were unsatisfactory.

Surveillance of mortality and cancer incidence among Swedish graphite electrode workers.

Mortality and cancer incidence were investigated among 901 workers at a Swedish company manufacturing graphite electrodes. Current and previous measurements of personal exposure to benzo[a]pyrene were used to calculate individual exposure estimates. Smoking habits were investigated by questionnaire. There were 42 deaths during the study period (1968-1989), whereas 32.3 would be expected, based on age, sex, time, and county-specific population statistics. Three cancers of the respiratory system were found vs 1.2 expected. The overall mortality was slightly elevated, mainly due to an increased number of deaths from external causes. Thus far, no excess risk of cancer has been documented in this cohort. The results indicate that an increased risk of respiratory cancer may be present, but influence from chance cannot be ruled out due to small numbers. The cohort will be under continued surveillance.

Formation of N-mononitrosopiperazine in the stomach and its excretion in the urine after oral intake of piperazine.

Piperazine, a secondary amine widely used as an anthelmintic drug, nitrosates rapidly in vitro to form two N-nitrosamines. Anhydrous piperazine and a drug formulation were found to have a content of 0.2 to 20 micrograms of the suspected carcinogen N-mononitrosopiperazine per gram piperazine, but no detectable amounts of the carcinogen N,N'-dinitrosopiperazine. The aim of this study was to investigate the possible nitrosation of the drug piperazine in man. Thirty minutes after oral administration of 480 mg piperazine to four fasting, healthy, male volunteers, gastric juice contained 140 to 230 micrograms/liter N-mononitrosopiperazine as determined by gas chromatography-thermal energy analysis. The total amount produced by endogenous formation in the stomach is estimated to have been 30 to 66 micrograms. N-Mononitrosopiperazine was not detected in blood, but was excreted in the urine, mainly in the first 6 hr (0.07 to 2.1 micrograms) with half of this appearing within 3 hr. Internal acidification of the urine did not affect the excretion or content. N,N'-Dinitrosopiperazine was not found in any sample of gastric juice, blood, or urine. The excretion of piperazine was in accordance with earlier findings. Coadministration of 2 g ascorbic acid resulted in a significant but incomplete and varying inhibition of both the nitrosation in the stomach and the excretion in urine.

Mortality and cancer incidence in Swedish battery workers exposed to cadmium and nickel.

OBJECTIVE: To follow up cancer incidence and mortality in a group of Swedish battery workers exposed to nickel hydroxide and cadmium oxide. METHODS: 869 workers, employed at least one year between the years 1940 and 1980 were followed up until 1992. Vital status and causes of death were obtained from the Swedish cause of death registry. Cancer morbidity was retrieved from the Swedish cancer registry. Regional reference rates were used to compute the expected numbers of deaths and cancers. RESULTS: Up to 31 December, 1992, a total of 315 deaths (292 in men and 23 in women) had occurred in the cohort. For men, the overall standardised mortality ratio (SMR) was 106 (95% confidence interval (95% CI) 93.7 to 118) and for women 83.8 (95% CI 53.1 to 126). The SMRs for total cancer mortality were 125 (95% CI 98.2 to 157) for men and 69.5 (95% CI 25.5 to 151) for women. The SMR for lung cancer in men was 176 (95% CI 101 to 287). No lung cancers were found among female workers. Up to 31 December, 1991, a total of 118 cancers had occurred in the cohort. A significantly increased standardised incidence ratio (SIR) was found for cancer of the nose and nasal sinuses in men, three cases v 0.36 expected, yielding an SIR of 832 (95% CI 172 to 2430). Applying a 10 year latency period in cohort members exposed to > or = 1000 micrograms cadmium/m3, the SIR was 1107 (95% CI 134 to 4000). Similarly, for cohort members exposed to 2000 micrograms nickel/m3, the SIR was 1080 (95% CI 131 to 3900). CONCLUSION: There was an increased overall risk for lung cancer, but no exposure-response relation between cumulative exposure to cadmium or nickel and risk of lung cancer. There was a highly significant increased risk of cancer of the nose and nasal sinuses, which may be caused by exposure to nickel or cadmium or a combination of both exposures.

Exposure to chemical agents in Swedish aluminum foundries and aluminum remelting plants--a comprehensive survey.

Secondary aluminum melting is mainly performed in sand, die, and static die-casting foundries and remelting plants. In seven Swedish foundries and two remelting plants, the exposure and area concentrations of total dust, metals, organic gases, and vapors were determined mainly as daily, time-weighted averages (TWAs). For most combinations of jobs and agents, the exposure levels were well below the current threshold limits suggested by the American Conference of Governmental Industrial Hygienists (ACGIH). However, high exposure levels of mineral oil mist (geometric mean [GM] = 0.6 mg/m3) were observed in the die-casting process, with a maximum of 4 mg/m3. The findings were similar for total dust (GM = 5.1 mg/m3) and crystalline quartz (GM = 0.05 mg/m3) during molding operations in the sand foundries, maximum air concentrations being 31 mg/m3 and 0.22 mg/m3, respectively. Other agents which occasionally reached high exposure levels included furfuryl alcohol (up to 23 mg/m3 during furan binder use in sand foundries), aniline (up to 2.6 mg/m3 during thermal degradation of cold-box binders), and dimethylethylamine (up to 9 mg/m3) in the cold-box process used in static die-casting and sand foundries. The average aluminum exposure levels (GM = 0.043 mg/m3) were low in all foundries, individual values not exceeding 0.94 mg/m3. The exposures to metals were below 10 percent of their threshold limits. Similarly low levels were detected of polyaromatic hydrocarbons, phenol, formaldehyde, methylenebisphenyl diisocyanate, and phenylisocyanate. In the aluminum remelting plants, a few high exposure levels of total dust (GM = 1.4 mg/m3) up to 8 mg/m3 were detected in furnace workers. Aluminum and other metals were well below 10 percent of their threshold limits, with the exception of a few high concentrations of manganese, up to 0.14 mg/m3. The between-worker variability (GSDB) in the foundries for total dust, aluminum, and oil mist were on the order of 3-4. The heterogenicity of secondary aluminum melting requires assessment of a wide variety of chemical agents. For certain exposures, technical and medical monitoring programs are still needed.