Pernilla Wiebert

Negligible clearance of ultrafine particles retained in healthy and affected human lungs

Ambient particles are believed to be a specific health hazard, although the underlying mechanisms are not fully understood. There are data in the literature indicating fast and substantial systemic uptake of particles from the lung. The present authors have developed an improved method to produce ultrafine particles with more stable radiolabelling and defined particle size range. Fifteen subjects inhaled technetium 99m (99mTc)-labelled carbonaceous particles of 100 nm in size. Radioactivity over the lung was followed for 70 h. The clearance of these ultrafine particles from the lungs and specifically translocation to the circulation was tested. Lung retention for all subjects at 46 h was mean±sd 99±4.6%. Cumulative leaching of 99mTc activity from the particles was 2.6±0.96% at 70 h. The 24-h activity leaching in urine was 1.0±0.55%. No evidence of a quantitatively important translocation of 100-nm particles to the systemic circulation from the lungs was found. More research is needed to establish if the ∼1% cleared activity originates from leached activity or insoluble translocated particles, and whether a few per cent of translocated particles is sufficient to cause harmful effects.

No Significant Translocation of Inhaled 35-nm Carbon Particles to the Circulation in Humans

Human pulmonary retention of 35 nm 99mTc-labeled carbonaceous particles, produced with a modified Technegas generator, was followed for 24 h using a gamma camera imaging technique. Nine healthy subjects and four asthmatics inhaled the test particles. Particle labeling stability was tested in vitro during 48 h. We also measured in vivo leaching in blood and in urine for 24 h. One additional subject was exposed to particles with unstable labeling. There were no significant differences between healthy and asthmatic subjects in any of the parameters studied. Particle retention after 24 h was 102% (SD ± 4.7). Cumulative in vitro leaching of 99mTc activity from the particles was 1.7% (±1.1) after 24 h. In blood samples, 80 min after exposure, 1.1% (± 0.4) of initially deposited activity was detected and 91% of the activity was not bound to particles. In urine sampled during the first 24 h after exposure, 3.6% (± 0.9) of lung deposited activity was detected. Lung retention was 30% after 1 h in the subject exposed to the leaching aerosol (n = 1). Thirty-one percent of the deposited activity was detected in the blood after 80 min and 80% was not bound to particles. Fifty percent of the activity was excreted with urine within 24 h. On gamma camera images the activity visibly translocated from lungs to thyroid and gastrointestinal tract. In conclusion, over a 24-h period there was no significant translocation of inhaled 35-nm particles to the systemic circulation.

Mortality, morbidity and occupational exposure to airway-irritating agents among men with a respiratory diagnosis in adolescence.

Objectives: To examine the influence of an airway diagnosis in adolescence on future health and occupation in Swedish men. Methods: Data were collected from the linkage of four Swedish national registers: the Military Service Conscription Register, the Population and Housing Censuses, the Inpatient Care Register and the National Cause of Death Register. A job-exposure matrix for airway-irritating substances was developed for application on the conscription cohort. The cohort included 49 321 Swedish men born 1949–51. Three groups—(1) healthy, (2) asthmatics (mild and severe asthma) and (3) subjects with allergic rhinitis without concurrent asthma—were identified at conscription and analysed for mortality, in-patient care and strategies for choice of occupation with emphasis on airway-irritating job exposure. Analyses were adjusted for smoking and childhood socioeconomic position. Results: The prevalence of total asthma was 1.8%, severe asthma 0.45% and allergic rhinitis 2.7%. Mortality for all causes was significantly higher in total asthma, hazard ratio (HR) 1.49 (95% CI 1.00 to 2.23), and lower in allergic rhinitis, HR 0.52 (95% CI 0.30 to 0.91). Asthma was a risk factor for inpatient care while allergic rhinitis was associated with less in-patient care (odds ratio (OR) for total asthma 1.16 (95% CI 1.00 to 1.34), severe asthma 1.38 (95% CI 1.04 to 1.85), allergic rhinitis 0.92 (95% CI 0.82 to 1.03)). Those with asthma tended to avoid jobs with a high probability for airway-irritating exposure (OR 0.88, 95% CI 0.71 to 1.09), but not to the same extent as subjects with allergic rhinitis (OR 0.58, 95% CI 0.47 to 0.70) (ORs from 1990). Conclusion: Subjects with asthma did not change their exposure situation to the same extent as subjects with allergic rhinitis. Further, asthmatics had an increased risk for morbidity and mortality compared to healthy subjects and subjects with allergic rhinitis.

Occupational exposures and the risk of amyotrophic lateral sclerosis.

Objectives To examine the associations of specific occupations and occupational exposures with the risk of amyotrophic lateral sclerosis (ALS) in the Swedish population. Methods A nested case–control study was conducted in Sweden. Patients with ALS diagnosed during 1991–2010 (n=5020) were identified from the National Patient Register and 5 controls per case (n=25 100) were randomly selected from the general Swedish population, individually matched to cases by birth year and sex. Occupational history was obtained from the Swedish censuses in 1970, 1980 and 1990. The Nordic Occupational Cancer Study Job Exposure Matrix was used to identify exposures related to individual occupations. Conditional logistic regression was used to estimate ORs and their 95% CIs. Results Higher risk of ALS was associated with precision-tool manufacturing (OR 1.68, 95% CI 1.11 to 2.52) and glass, pottery and tile work (OR 1.76, 95% CI 1.03 to 3.00), whereas lower risk was associated with textile work (OR 0.44, 95% CI 0.21 to 0.91). None of the examined occupational exposures were associated with ALS risk overall. However, among individuals younger than 65 years of age, an association with a higher risk of ALS was found for formaldehyde (OR 1.29, 95% CI 1.00 to 1.65), and an association with a lower risk of ALS was found for methylene chloride (OR 0.49, 95% CI 0.26 to 0.93). Conclusions We identified several occupations and occupational exposures that may be associated with the risk of ALS in Sweden. Occupational history obtained from censuses every 10 years remains a limitation of the study.

Occupational exposure to particles and incidence of acute myocardial infarction and other ischaemic heart disease.

Background Ambient particulate air pollution has been linked to cardiovascular disease. Occupational particle exposure levels may be several times higher than ambient levels but has been less studied. Objectives The authors investigated the association between occupational exposure to particles and the incidence of ischaemic heart disease (IHD). Methods The cohort included all manual workers in the Swedish national census of 1980 with information on demographic data and occupation. Information on hospital admissions for acute myocardial infarction or other IHDs and cause of death were obtained from nation-wide registers. A job-exposure matrix for exposure to small (<1 μm) and large (>1 μm) particles was developed. HRs were calculated with Cox regression with adjustment for sex, age, socioeconomic group and urban/rural residential area. Results Exposure to small particles was associated with an increased HR for acute myocardial infarction of 1.12 (95% CI 1.09 to 1.15), and HR for exposure to large particles was 1.14 (95% CI 1.10 to 1.18). The association was somewhat stronger for workers exposed to small particles for more than 5 years, 1.21 (95% CI 1.11 to 1.31), but no trend with exposure intensity was found. The risk associated with exposure to small particles was higher among women than among men, 1.30 (95% CI 1.12 to 1.51) and 1.10 (95% CI 1.07 to 1.14), respectively. Findings were essentially similar for other IHDs. Conclusions This explorative study gives some support to the hypothesis that occupational exposure to particles increases the risk of acute myocardial infarction and other IHD. The findings must be interpreted cautiously due to lack of smoking data.

Occupational Exposure to Electric Shocks and Magnetic Fields and Amyotrophic Lateral Sclerosis in Sweden

Background: Amyotrophic lateral sclerosis (ALS) has been consistently related to “electric occupations,” but associations with magnetic field levels were generally weaker than those with electrical occupations. Exposure to electric shock has been suggested as a possible explanation. Furthermore, studies were generally based on mortality or prevalence of ALS, and studies often had limited statistical power. Methods: Using two electric shock and three magnetic field job-exposure matrices, we evaluated the relationship of occupational magnetic fields, electric shocks, electric occupations, and incident ALS in a large population-based nested case–control study in Sweden. Subanalyses, specified a priori, were performed for subjects by gender and by age (less than and more than 65 years). Results: Overall, we did not observe any associations between occupational magnetic field or electric shock exposure and ALS. For individuals less than 65 years old, high electric shock exposure was associated with an odds ratio (OR) of 1.22 (95% confidence interval [CI] = 1.03, 1.43). The corresponding result for the age group 65 years or older was OR = 0.92 (95% CI = 0.81, 1.05). Results were similar regardless which job exposure matrices, exposure definitions, or cutpoints were used. For electric occupations, ORs were close to unity, regardless of age. For welders, no association was observed overall, although for welders <65 years the OR was 1.52 (95% CI = 1.05, 2.21). Conclusions: In this very large population-based study based on incident ALS case subjects, we did not confirm previous observations of higher risk of ALS in electrical occupations, and provided only weak support for associations between electric shocks and ALS.

Testicular germ cell tumours and parental occupational exposure to pesticides: a register-based case–control study in the Nordic countries (NORD-TEST study)

Objectives A potential impact of exposure to endocrine disruptors, including pesticides, during intrauterine life, has been hypothesised in testicular germ cell tumour (TGCT) aetiology, but exposure assessment is challenging. This large-scale registry-based case–control study aimed to investigate the association between parental occupational exposure to pesticides and TGCT risk in their sons. Methods Cases born in 1960 or onwards, aged between 14 and 49 years, and diagnosed between 1978 and 2013 in Denmark, Finland, Norway or Sweden, were identified from the respective nationwide cancer registries. Four controls per case were randomly selected from the general national populations, matched on year of birth. Information on parental occupation was collected through censuses or Pension Fund information and converted into a pesticide exposure index based on the Finnish National Job-Exposure Matrix. Results A total of 9569 cases and 32 028 controls were included. No overall associations were found for either maternal or paternal exposures and TGCT risk in their sons, with ORs of 0.83 (95% CI 0.56 to 1.23) and of 1.03 (0.92 to 1.14), respectively. Country-specific estimates and stratification by birth cohorts revealed some heterogeneity. Cryptorchidism, hypospadias and family history of testicular cancer were risk factors but adjustment did not change the main results. Conclusions This is the largest study on prenatal exposure to pesticides and TGCT risk, overall providing no evidence of an association. Limitations to assess individual exposure in registry-based studies might have contributed to the null result.

Parental occupational exposure to heavy metals and welding fumes and risk of testicular germ cell tumors in offspring: A registry-based case-control study

Background: Data are scarce on the association between prenatal/preconception environmental exposure and testicular germ cell tumor (TGCT) in offspring. We examined parental occupational exposures to heavy metals and welding fumes in relation to TGCT in offspring in a registry-based case–control study (NORD-TEST Study). Methods: We identified TGCT cases diagnosed at ages 14–49 years in Finland (1988–2012), Norway (1978–2010), and Sweden (1979–2011) through nationwide cancer registries. These cases were individually matched by country and year of birth to controls selected from population registries. Information on parental occupations was retrieved from censuses. From this, we estimated prenatal/preconception exposures of chromium, iron, nickel, lead, and welding fumes (all three countries), and cadmium (Finland only) for each parent using job-exposure matrices specifying prevalence (P) and mean exposure level (L). Exposure indices were calculated as a product of P and L (P × L), and exposure categories were based on P × L or different combinations of P and L. Results: The study comprised 8,112 cases and 26,264 controls. We observed no statistically significant TGCT risk associated with presence of heavy metals/welding fumes (P × L > 0) and no dose-response relationship (Ptrend ≥ 0.32). A statistically significant elevated TGCT risk was found in paternal exposure category where both P and L of chromium were high (vs. no chromium; OR = 1.37, 95% confidence interval; 1.05–1.79). Conclusions: Our study provides little evidence of associations between parental exposures to heavy metals/welding fumes and TGCT in offspring with the potential exception of high paternal chromium exposure. Impact: Further research on paternal chromium exposure is warranted. Cancer Epidemiol Biomarkers Prev; 25(10); 1426–34. ©2016 AACR.

Occupation and Risk of Developing Rheumatoid Arthritis: Results From a Population-Based Case-Control Study

Environmental factors are of importance for the etiology of rheumatoid arthritis (RA), but much remains unknown concerning the contributions from distinct occupational hazards. We explored the association between occupation and the risk of anti–citrullinated protein antibody (ACPA)+ RA or ACPA− RA.

Airborne Occupational Exposures and Risk of Developing Rheumatoid Arthritis: A Job‐Exposure Matrix Approach in a Swedish Population‐Based Case–Control Study

Professor Alexis Descatha suggests that we should have used job-exposure matrices (JEM) to understand the underlying increased risks we noted between certain occupations and risk of rheumatoid arthritis (RA) in our study Occupation and Risk of Developing Rheumatoid Arthritis: Results From a Population-Based Case-Control Study (1). This article is protected by copyright. All rights reserved.