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ObjectivesThis study examined the association between night shift work and risk of breast cancer, overall and by hormone receptor subtype, among females in the Norwegian Offshore Petroleum Workers (NOPW) cohort. We also examined the association of coexposure (chlorinated degreasers and benzene) and breast cancer risk, and possible interaction with work schedule.DesignProspectively recruited case-cohort study within the NOPW cohort.SettingFemale offshore petroleum workers active on the Norwegian continental shelf.Participants600 female workers (86 cases and 514 non-cases) were included in the study. We excluded workers that died or emigrated before start of follow-up, had missing work history, were diagnosed with breast cancer or other prior malignancy (except non-melanoma skin cancer) before start of follow-up.ResultsNo overall association was found between breast cancer risk and work schedule (HR 0.87, 95% CI 0.52 to 1.46 for work schedule involving night shift vs day shift only). There was no significant association between work schedule and risk of any breast cancer subtype. No significant interactions were found between work schedule and chemical coexposures (breast cancer overall Pinteraction chlorinated degreasers=0.725 and Pinteraction benzene=0.175).ConclusionsOur results did not provide supporting evidence that work schedule involving night shift affects breast cancer risk in female offshore petroleum workers, but should be considered cautiously due to few cases. Further studies with larger sample sizes are warranted.

In a recent study we found that fathers’ but not mothers’ onset of overweight in puberty was associated with asthma in adult offspring. The potential impact on offspring’s adult lung function, a key marker of general and respiratory health, has not been studied. We investigated the potential causal effects of parents’ overweight on adult offspring’s lung function within the paternal and maternal lines. We included 929 offspring (aged 18–54, 54% daughters) of 308 fathers and 388 mothers (aged 40–66). Counterfactual-based multi-group mediation analyses by offspring’s sex (potential moderator) were used, with offspring’s prepubertal overweight and/or adult height as potential mediators. Unknown confounding was addressed by simulation analyses. Fathers’ overweight before puberty had a negative indirect effect, mediated through sons’ height, on sons’ forced expiratory volume in one second (FEV1) (beta (95% CI): −144 (−272, −23) mL) and forced vital capacity (FVC) (beta (95% CI): −210 (−380, −34) mL), and a negative direct effect on sons’ FVC (beta (95% CI): −262 (−501, −9) mL); statistically significant effects on FEV1/FVC were not observed. Mothers’ overweight before puberty had neither direct nor indirect effects on offspring’s lung function. Fathers’ overweight starting before puberty appears to cause lower FEV1 and FVC in their future sons. The effects were partly mediated through sons’ adult height but not through sons’ prepubertal overweight.

Introduction: Although quality of life is impaired in subjects with various lung diseases, the associations with objective measures of lung function have been reported to be weak. Objectives: To describe the association between lung function decline and impaired self-reported health-status in a large adult general population sample followed for 10 years. Methods: Associations between changes in lung function and the SF-36 Health Survey was investigated in 3,843 participants in the European Community Respiratory Health Survey (ECRHS) with complete data in the second (2002, age range 30-55 years) and third follow-up (2012). We estimated the association between change of maximum forced expired volume in 1 second (FEV1) and forced vital capacity (FVC) and change in each of the eight SF-36 health scales adjusting for sex, age and lung function at baseline. Results: Mean yearly change in FEV1 were 48 (standard deviation (SD) 30) ml in males and 40(22) ml in women. Corresponding changes in FVC were 40(38) and 31(30) ml. Increasing decline in FEV1 and FVC were highly significantly associated with reduced scores in the four scales predominantly measuring physical health at follow-up, but not the mental scales. A yearly decline of 50 ml in FEV1 was associated with a reduced score of 0.25 SD in physical functioning, 0.12 in role limitations due to physical problems, 0.10 in bodily pain and 0.24 in general perception of health. Conclusion: In a general population followed for 10 years, we found marked effects of lung function decline on the physical scales of the SF-36, but not on the mental scales. This indicates SF-36 scales as sensitive self-reported measures of changes in lung health. *Shared last authorship

Emerging research suggests environmental exposures before conception may adversely affect allergies and lung diseases in future generations. Most studies are limited as they have focused on single exposures, not considering that these diseases have a multifactorial origin in which environmental and lifestyle factors are likely to interact. Traditional exposure assessment methods fail to capture the interactions among environmental exposures and their impact on fundamental biological processes, as well as individual and temporal factors. A valid estimation of exposure preconception is difficult since the human reproductive cycle spans decades and the access to germ cells is limited. The exposome is defined as the cumulative measure of external exposures on an organism (external exposome), and the associated biological responses (endogenous exposome) throughout the lifespan, from conception and onwards. An exposome approach implies a targeted or agnostic analysis of the concurrent and temporal multiple exposures, and may, together with recent technological advances, improve the assessment of the environmental contributors to health and disease. This review describes the current knowledge on preconception environmental exposures as related to respiratory health outcomes in offspring. We discuss the usefulness and feasibility of using an exposome approach in this research, advocating for the preconception exposure window to become included in the exposome concept.

Background: An increasing number of low-molecular weight substances are identified that may cause hypersensitivity pneumonitis (HP). Hairdressers exposed to persulfates may present with work-related flu-like symptoms and shortness of breath rather than the typical asthmatic wheezy chest, and we speculate that persulfates might cause HP. Aims: To study to what extent hairdressers investigated with specific inhalation challenge test (SIC) fulfill published criteria for HP. Methods: Forty-two female hairdressers (median age 31 years) underwent SIC in an inhalation chamber, exposed on consecutive days to 150 g lactose powder (placebo) and increasing dose/time of potassium persulfate, administered by dust tipping from one tray to another. A positive response of asthma was defined as two subsequent measures of FEV1 ≤15% of baseline. HP was defined according to criteria by Morell F, 2008, based on measurements of DLCO, FVC, temperature, white blood cell count, oxygen tension on physical exercise and symptoms of general malaise. Results: Thirty-two persons filled the criteria for asthma and/or HP on provocation with persulfates. Nine had asthma only, 7 had HP only and 16 filled the criteria for both. Among these patients, 90% presented with shortness of breath, 86% with rhinitis, and 43% with wheeze. In patients who fulfilled HP criteria, fall in FVC and DLCO, and increased neutrophils were the most common characteristics. Conclusion: A large number of hairdressers filled criteria for HP diagnosed with SIC, and persulfate related airways disease in hairdressers need further study.

Background: Excess skin cancer mortality and incidence have been reported among both land-based and offshore petroleum workers. The association between skin cancer and ultraviolet radiation (UVR) exposure has not been examined in these workers, although they have long off-duty periods and high average income that may allow travelling to sunny destinations. In addition, they have access to solariums free of charge on many accommodation platforms. Aims: To prospectively examine risk of incident cutaneous melanoma (CM) and non-melanoma skin cancer (NMSC), according to sun-tanning habits with adjustment for aromatic hydrocarbon exposure. Methods: A cohort of men employed offshore from 1965 to 1999 was linked through the Cancer Registry of Norway 1999–2012. Cox regression adapted to a stratified case-cohort design was used to estimate hazard ratios with 95% confidence intervals. Results: The cohort included 24917 men. During 13.5 years of follow-up, 112 CMs and 70 NMSCs occurred. A positive dose–response relationship was seen between sunburn frequency and risk of CM (Ptrend < 0.05) and NMSC (Ptrend < 0.01). Solarium use both before and after age 20 was related to increased risk of NMSC. Sunscreen use was associated with increased risk of NMSC (Ptrend < 0.001). Conclusions: UVR exposure seems to be a significant contributor to the elevated risk of skin cancer observed in North Sea offshore workers. The positive association between solarium use and NMSC risk adds to the growing body of literature on artificial UV devices as carcinogenic. This research has been published in Occupational Medicine. © 2017 Oxford University Press

Background: We prospectively examined skin cancer risk according to occupational exposure to aromatic hydrocarbons with adjustment for ultraviolet radiation exposure, in a cohort of 24 917 male offshore petroleum workers. Methods: Hazard ratios (HRs) and 95% confidence intervals were estimated with Cox regression adapted to a stratified case‐cohort design. Results: During 13.5 years of follow‐up, 112 cutaneous melanomas (CMs) and 70 non‐melanoma skin cancers were identified. Increased risks of CM and of squamous cell carcinoma on the forearm and hand were seen among those ever exposed to crude oil or benzene. For skin cancers of the forearm and hand combined, cumulative and duration metrics of benzene exposure showed Ptrends of 0.031 and 0.003, respectively. Conclusions: Our results support an association between exposure to crude oil or benzene and skin cancer risk on hands and forearms among offshore petroleum workers. Dermal uptake of polycyclic aromatic hydrocarbons or benzene may explain this association. This research has been published in the American Journal of Industrial Medicine. © 2017 Wiley

Publisher's version (útgefin grein)., Background: Overweight status and asthma have increased during the last decades. Being overweight is a known risk factor for asthma, but it is not known whether it might also increase asthma risk in the next generation. Objective: We aimed to examine whether parents being overweight in childhood, adolescence, or adulthood is associated with asthma in their offspring. Methods: We included 6347 adult offspring (age, 18-52 years) investigated in the Respiratory Health in Northern Europe, Spain and Australia (RHINESSA) multigeneration study of 2044 fathers and 2549 mothers (age, 37-66 years) investigated in the European Community Respiratory Health Survey (ECRHS) study. Associations of parental overweight status at age 8 years, puberty, and age 30 years with offspring's childhood overweight status (potential mediator) and offspring's asthma with or without nasal allergies (outcomes) was analyzed by using 2-level logistic regression and 2-level multinomial logistic regression, respectively. Counterfactual-based mediation analysis was performed to establish whether observed associations were direct or indirect effects mediated through the offspring's own overweight status. Results: We found statistically significant associations between both fathers' and mothers' childhood overweight status and offspring's childhood overweight status (odds ratio, 2.23 [95% CI, 1.45-3.42] and 2.45 [95% CI, 1.86-3.22], respectively). We also found a statistically significant effect of fathers' onset of being overweight in puberty on offspring's asthma without nasal allergies (relative risk ratio, 2.31 [95% CI, 1.23-4.33]). This effect was direct and not mediated through the offspring's own overweight status. No effect on offspring's asthma with nasal allergies was found. Conclusion: Our findings suggest that metabolic factors long before conception can increase asthma risk and that male puberty is a time window of particular importance for offspring's health., This study was funded by the European Union's Horizon 2020 research and innovation program as part of the ALEC study (Ageing Lungs in European Cohorts study, grant no. 633212). The RHINESSA generation study also received funding by the Research Council of Norway (grant nos. 214123 and 228174), the Bergen Medical Research Foundation (Norway), the Western Norwegian Regional Health Authorities (grant nos. 912011, 911892, and 911631), the Norwegian Labour Inspection, the Norwegian Asthma and Allergy Association, the Danish Woods Foundation (grant no. 444508795), the Danish Working Environment Authority (grant no. 20150067134), the Swedish Lung Foundation, the Swedish Asthma and Allergy Association, and the Estonian Research Council (grant no. PUT562). The funding agencies had no direct role in the conduct of the study; the collection, management, statistical analysis, and interpretation of the data; and the preparation or approval of the manuscript.

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Background Occupational eosinophilic bronchitis (OEB) has been described only as anecdotal case reports. Objective We investigated the clinical and inflammatory characteristics of subjects with OEB identified in a cohort of subjects who completed a specific inhalation challenge (SIC) with occupational agents. Methods In this retrospective multicenter study, OEB was defined by (1) a fall in FEV1 less than 15% during the SIC and the absence of nonspecific bronchial hyperresponsiveness both before and after the SIC and (2) a postchallenge increase of 3% or more in sputum eosinophils. The subjects who fulfilled these criteria were compared with 226 subjects with a negative SIC and 30 subjects with a positive SIC who failed to show baseline nonspecific bronchial hyperresponsiveness. Results An isolated increase in postchallenge sputum eosinophils was documented in 33 of 259 subjects (13%) with a negative SIC. These subjects reported significantly more often an isolated cough at work compared with the negative and positive SIC controls. When compared with positive SIC controls, the subjects with OEB experienced less frequently work-related wheezing and reported a shorter duration of symptoms at work. The sensitivity of the post-SIC increase in fractional exhaled nitric oxide in identifying OEB among subjects with a negative SIC was low, ranging from 43% to 24% using cutoff values of 8 ppb to 17.5 ppb, whereas the specificity was high (90%-97%). Conclusions This study highlights the relevance of induced sputum analysis in the investigation of work-related asthma symptoms to identify isolated increases in sputum eosinophils that are consistent with a diagnosis of OEB.

BACKGROUND: While acrylates are well-known skin sensitizers, they are not classified as respiratory sensitizers although several cases of acrylate-induced occupational asthma (OA) have been reported.OBJECTIVE: To evaluate the characteristics of acrylate-induced OA in a large series of cases and compare those with OA induced by other low-molecular-weight (LMW) agents.METHODS: Jobs and exposures, clinical and functional characteristics, and markers of airway inflammation were analyzed in an international, multicenter, retrospective cohort of subjects with OA ascertained by a positive inhalation challenge to acrylates (n = 55) or other LMW agents (n = 418) including isocyanates (n = 125).RESULTS: Acrylate-containing glues were the most prevalent products, and industrial manufacturing, dental work, and beauty care were typical occupations causing OA. Work-related rhinitis was more common in acrylate-than in isocyanate-induced asthma (P < .001). The increase in postchallenge fractional exhaled nitric oxide was significantly greater in acrylate-induced OA (26.0; 8.2 to 38.0 parts per billion [ppb]) than in OA induced by other LMW agents (3.0; -1.0 to 10.0 ppb; P < .001) or isocyanates (5.0; 2.0 to 16.0 ppb; P = .010). Multivariable models confirmed that OA induced by acrylates was significantly and independently associated with a postchallenge increase in fractional exhaled nitric oxide (≥17.5 ppb).CONCLUSIONS: Acrylate-induced OA shows specific characteristics, concomitant work-related rhinitis, and exposure-related increases in fractional exhaled nitric oxide, suggesting that acrylates may induce asthma through different immunologic mechanisms compared with mechanisms through which other LMW agents may induce asthma. Our findings reinforce the need for a reevaluation of the hazard classification of acrylates, and further investigation of the pathophysiological mechanisms underlying their respiratory sensitizing potential.

Benzene, toluene, ethylbenzene, xylenes, naphthalene and n-hexane evaporating from a thin oil film was measured for 30 min in a small-scale test system at 2 and 13 °C and the impact of physicochemical properties on airborne benzene with time after bulk oil release was studied. Linear mixed-effects models for airborne benzene in three time periods; first 5, first 15 and last 15 min of sampling, indicated that benzene content in fresh oil, oil group (condensate/light crude oil) and pour point were significant determinants explaining 63–73% of the total variance in the outcome variables. Oils with a high pour point evaporated considerably slower than oils with a low pour point. The mean air concentration of total volatile organic compounds was significatly higher at 13 °C (735 ppm) compared to 2 °C (386 ppm) immediately after release of oil, but at both temperatures the concentration rapidly declined. acceptedVersion

We aimed to characterize bakers' personal exposure to airborne flour dust with respect to the health-related aerosol fractions inhalable, extrathoracic, and thoracic dust, and to examine possible production-related determinants of dust exposure. Sixty-eight bakers from 7 bakeries in Bergen, Norway (2009-2012) participated in the exposure assessment, comprising full-shift personal samples of inhalable dust (n = 107) and thoracic dust (n = 61). The relation between possible determinants and exposure was estimated using mixed effects models, while associations between the various aerosol fractions across task groups and type of bakeries were described by Pearson's correlation coefficients. Bakers' overall geometric mean personal exposure to inhalable, extrathoracic, and thoracic dust were 2.6 mg/m3 (95% CI: 2.0, 3.2), 2.2 mg/m3 (95% CI: 1.9, 2.7), and 0.33 mg/m3 (95% CI 0.3, 0.4), respectively. A total of 29% of the measurements of inhalable dust were above the Norwegian Occupational Exposure Limit of 3 mg/m3. The exposure variability of inhalable dust could not be explained by any of the examined production-related determinants, while the daily production volume explained 18% of the variance in thoracic dust exposure. Overall, the thoracic dust represented 15% of the inhalable dust, being rather stable across the production-related determinants. The overall correlation between inhalable and thoracic dust was nevertheless moderate (r = 0.52, p < 0.001), with the highest correlation for craft bakers (r = 0.62) and no correlation during dough forming (r = 0.01). Bakers are exposed to flour dust at a level that most likely represents an excess risk of developing chronic diseases of the respiratory system, and a decrease of present exposure level is imperative. Extrathoracic dust-likely the most relevant sub-fraction in respect to flour-induced sensitization and occupational rhinitis-represented the main proportion of the measured inhalable dust. The variation in correlation coefficients between the dust fractions across bakery types and task groups underlines the need of more knowledge about how these aerosol fractions are distributed across the production process and bakery types.

Objectives An employee with no prior history of allergy or asthma, experienced respiratory and flu-like symptoms during production of shrimp shell powder in a seafood savory factory in Norway. We aimed to clarify the diagnosis and to identify the cause of the symptoms by specific inhalation challenge (SIC) and by characterizing the powder's biocontaminants, particle size fractions and inflammatory potential. Methods Respiratory and immunological responses were measured the day before and after each of four challenges with 20–150 g shrimp shell powder during three consecutive days. The powder was analyzed for endotoxin, microorganisms and particle size fractions by standardized laboratory methods. Total inflammatory potential was quantified by reactive oxygen species (ROS) production in a granulocyte assay. Results The patient had elevated IgG, but not IgE, towards shrimp shell powder. 20 min challenge with 150 g shrimp shell powder induced 15% decrease in FVC, 23% decrease in FEV 1 and increased unspecific bronchial reactivity by methacholine. Neutrophils and monocytes increased 84% and 59%, respectively, and the patient experienced temperature increase and flu-like symptoms. The shrimp shell powder contained 1118 endotoxin units/g and bacteria including Bacillus cereus , and 57% respirable size fraction when aerosolized. The ROS production was higher for shrimp shell powder than for endotoxin alone. Conclusions Endotoxin and other bacterial components combined with a high fraction of respirable dust might be the cause of the symptoms. The patient's characteristics and response to SIC were best compatible with occupational asthma and organic dust toxic syndrome, while hypersensitivity pneumonitis could not be excluded.

BACKGROUND: Although sensitizer-induced occupational asthma (OA) accounts for an appreciable fraction of adult asthma, the severity of OA has received little attention. OBJECTIVE: The aim of this study was to characterize the burden and determinants of severe OA in a large multicenter cohort of subjects with OA. METHODS: This retrospective study included 997 subjects with OA ascertained by a positive specific inhalation challenge completed in 20 tertiary centers in 11 European countries during the period 2006 to 2015. Severe asthma was defined by a high level of treatment and any 1 of the following criteria: (1) daily need for a reliever medication, (2) 2 or more severe exacerbations in the previous year, or (3) airflow obstruction. RESULTS: Overall, 162 (16.2%; 95% CI, 14.0%-18.7%) subjects were classified as having severe OA. Multivariable logistic regression analysis revealed that severe OA was associated with persistent (vs reduced) exposure to the causal agent at work (odds ratio [OR], 2.78; 95% CI, 1.50-5.60); a longer duration of the disease (OR, 1.04; 95% CI, 1.00-1.07); a low level of education (OR, 2.69; 95% CI, 1.73-4.18); childhood asthma (OR, 2.92; 95% CI, 1.13-7.36); and sputum production (OR, 2.86; 95% CI, 1.87-4.38). In subjects removed from exposure, severe OA was associated only with sputum production (OR, 3.68; 95% CI, 1.87-7.40); a low education level (OR, 3.41; 95% CI, 1.72-6.80); and obesity (OR, 1.98; 95% CI, 0.97-3.97). CONCLUSIONS: This study indicates that a substantial proportion of subjects with OA experience severe asthma and identifies potentially modifiable risk factors for severe OA that should be targeted to reduce the adverse impacts of the disease. (C) 2019 Published by Elsevier Inc. on behalf of the American Academy of Allergy, Asthma & Immunology

Background: Little is known on outdoor air pollution in a long-term perspective and societal costs such as sick leave. In the Nordic countries, recent pollution health impact assessments have had t ...

Background: We found that a father’s overweight in puberty was associated with non-allergic asthma in his future offspring.Aim: We explored the associations of both fathers and their offsprings own ...

Objectives The main aim of this study was to assess the biological uptake of benzene and polycyclic aromatic hydrocarbons (PAHs) for subjects exposed to fresh crude oil released at sea. Methods: The study included 22 subjects participating in an ‘oil-on-water’ field trial in the North Sea. Over 2 consecutive days, there were six releases with two different types of fresh crude oils. Exposed subjects (n = 17) were either located in small, open-air boats downwind and close to the released oil (

Introduction Oil spill cleanup personnel could be exposed to benzene during cleanup of accidental spill of crude oil at sea. S-Phenyl Mercapturic Acid (SPMA) is reported to be a sensitive urinary marker of exposure to low levels of benzene, but there is a lack of information on biological uptake of benzene during cleanup of oil spills. The aim of this study was to investigate the exposure to benzene during an oil spill by measuring the concentration of SPMA in urine for subjects participating in an oil spill field trial at sea. Methods The study included 22 subjects taking part in an oil spill field trial in the North Sea with two types of fresh crude oil. The subjects were located in open air sampling boats close to the oil slick ( Results SPMA was not detected in the urine samples of subjects wearing protective masks and in the control group. Among the six subjects who reported not to wear protective masks during the spill the concentration of SPMA in urine ranged 0.5–3.3 µmol/mol. They were all located in the boat closest to the oil spill. Discussion We have previously reported that mean personal exposure to benzene in air was 0.43 ppm for the personnel in the boat closest to the oil spill. The present study suggests that work with fresh oil spilled at sea might cause biological uptake of benzene. Appropriate personal respiratory protection should be used to prevent such uptake.

Altered gene expression in pathways relevant to leukaemogenesis, as well as reduced levels of circulating lymphocytes, have been reported in workers that were exposed to benzene concentrations below 1 ppm. In this study, we analysed whole blood global gene expression patterns in a worker cohort with altered levels of T cells and immunoglobulins IgM and IgA at three time points, pre-shift, post-shift (after three days), and post-recovery (12 hours later). Eight benzene exposed tank workers performing maintenance work in crude oil cargo tanks with a mean benzene exposure of 0.3 ppm (range 0.1&ndash, 0.5 ppm) and five referents considered to be unexposed were examined by gene expression arrays. By using our data as independent validation, we reanalysed selected genes that were reported to be altered from previous studies of workers being exposed to sub-ppm benzene levels Four out of six genes previously proposed as marker genes in chronically exposed workers separated benzene exposed workers from unexposed referents (CLEC5, ACSL1, PRG2, IFNB1). Even better separation of benzene exposed workers and referents was observed for short-term exposure for genes in the Jak-STAT pathway, particularly elevated expression of IL6 and reduced expression of IL19.

Background: In the prospective population-based Norwegian Mother and Child Cohort Study (MoBa), comprising 113 754 offspring, we investigated the association between parental exposure to “gasoline or exhaust”, as a proxy for benzene exposure, and childhood leukaemia. Methods: Around gestational week 17, mothers and fathers responded to a questionnaire on exposure to various agents during the last 6 months and 6 months pre-conception, respectively. Benzene exposure was assessed through self-reported exposure to “gasoline or exhaust”. Cases of childhood leukaemia (n = 70) were identified through linkage with the Cancer Registry of Norway. Risk was estimated by hazard ratios (HRs) with 95% confidence intervals (95%CI), comparing offspring from exposed and unexposed parents using a Cox regression model. Results: Maternal exposure to "gasoline or exhaust" was associated with an increased risk of childhood leukaemia (HR = 2.59; 95%CI: 1.03, 6.48) and acute lymphatic leukaemia (HR = 2.71; 95%CI: 0.97, 7.58). There was an increasing risk for higher exposure (p value for trend = 0.032 and 0.027). The association did not change after adjustment for maternal smoking. Conclusion: In spite of rather few cases, the findings in this prospective study, with the exposure metric defined a priori, support previous observations relating maternal exposure to benzene from gasoline and other petroleum-derived sources and the subsequent development of childhood leukaemia in the offspring.

Background: Overweight in pregnancy has been linked to offspring asthma, but whether this is partly related to overweight in the mother before conception has not been reported. Aim: To examine if mothers’ overweight in childhood, adolescence and adulthood increase the risk of overweight and asthma in her offspring. Methods: We evaluated 3522 adult offspring (age 18-52 yrs.) of 2547 mothers (age 39-65 yrs.) from the RHINESSA generation study (10 centres in North Europe, Spain and Australia). The association of mothers9 overweight assessed through self-reported body silhouette at ages 8, menarche and 30, with allergic/non-allergic asthma in offspring, was analysed using a cluster robust 2-level 2→2→1 mediation model, adjusting for overweight, asthma, smoking and education in grandparents and fathers; age, asthma, smoking and education in mothers; and overweight, sex and age in offspring. Results: 9.5% and 7.0% of offspring reported allergic and non-allergic asthma, respectively. 21.3 % of the mothers reported overweight at age 8, 7.6% at menarche and 14.6% at age 30 (before offspring’s birth). OR. Odds Ratio; RRR, Relative Risk Ratio Conclusion: Mothers’ overweight starting in childhood or before menarche was associated with offspring overweight in childhood, but not with offspring asthma (Funding: H2020 EU grant No 633212).

Objective: A fish-processing worker reporting symptoms consistent with HP during slaughtering of salmon was referred to our clinic. The 42 year old man, never smoker, no history of allergy or respiratory disease, reported job-related symptoms for the last 3 years (dyspnoe, coughing, flu-like symptoms and fever). The symptoms started 3-4 hours after start of work shift. He felt better next morning and during weekends. The last year he had had recurrent episodes of pneumonia. Aim: By the use of specific inhalation challenge (SIC), we aimed to describe the patient´s respiratory, clinical and immunological responses after inhalation of salmon proteins. Method: SIC is a method for diagnosing occupational asthma and a modified version of the protocol is used for diagnosing hypersensitivity pneumonitis (HP). The challenge with salmon proteins was conducted in a provocation chamber (13 m3) with the patient manually filleting salmon (20 min). Results: At baseline there was a tendency of low diffusion capacity for carbon monoxide (DLCO 74% of predicted), lung function verging a restrictive pattern (FVC 80% of predicted), and no specific IgEs towards fish allergens. In response to SIC, he got flu-like symptoms, further decrease in FVC (12.5%) and DLCO (11%), increase in neutrophils (12%) and decrease in lymphocytes (23%), as compared to pre-test values. Next day the patient was asymptomatic, and FVC and DLCO were normalized to pre-test values. Conclusion: The patient’s response to salmon proteins was compatible with HP according to Munoz X et al [Curr Opin Allergy Clin Immunol. 2013;13:151-8]. A better awareness of etiological factors of HP other than birds and mold is needed.

Background: Overweight is a known risk factor for personal asthma, but it is not known whether overweight may also increase asthma risk in the next generation. Aim: To examine if fathers’ overweight in childhood, adolescence or adulthood is associated with offspring asthma. Methods: We included adult offspring (n=2818, mean age range 18-50 yrs) from the RHINESSA generation study including centres in Norway, Denmark, Iceland, Sweden, Estonia, Spain and Australia with fathers (n=2041, age range 37-66 yrs) studied in ECRHS/RHINE. Associations between allergic/non-allergic asthma in offspring and overweight assessed through self-reported body size in childhood (age 8), adolescence (voice break) and adulthood (age 30) was analysed using cluster-robust 2-level 2→2→1 mediation models. We adjusted for overweight, asthma, smoking and education in grandparents and mothers; age, asthma, smoking and education in fathers; and overweight, sex and age in offspring. Results: A total of 8.5% and 7.9% of offspring reported allergic and non-allergic asthma, respectively. Fathers reported overweight with a prevalence of 9.8% at age 8, 2.3% at voice break and 6.4% at age 30 (pre-conception). In the mediation analysis, fathers’ overweight at voice break (but not in childhood or adulthood) was associated with offspring non-allergic asthma irrespective of offspring gender (relative risk ratio RRR = 2.29; 95%CI: 1.19, 4.41). No effect on offspring allergic asthma was found. Conclusion: Fathers’ overweight in adolescence is associated with and increased risk of offspring non-allergic asthma, suggesting that factors long before conception may affect asthma in future generations.

Introduction There is an established causal relationship between benzene exposure and acute myelogenous leukaemia in adults, but the association between parental benzene exposure and childhood leukaemia in offspring remains inconclusive. Objective Using the prospective population-based Norwegian Mother and Child Cohort Study (MoBa) comprising 1 13 754 offspring (1999–2009), we investigated the association between parental exposure to ”gasoline or exhaust” as a proxy to benzene exposure and childhood leukaemia. Method Around the 17th gestational week mothers and fathers responded to questions on a range of occupational exposures during the last 6 months and pre-conception, respectively. Exposure to benzene was assessed through self-reported exposure to ”gasoline or exhaust” (”never exposed”, ”ever exposed” and ”exposed>30 days”), the latter interpreted as being occupational. Development of subsequent childhood leukaemia (n=70) were identified through linkage with the Cancer Registry of Norway. The risk was estimated by odds ratios (OR) with 95% confidence intervals (95% CI) comparing the offspring from exposed and unexposed parents using a logistic regression model, adjusting for maternal smoking and birth weight. Results Maternal exposure was associated with an increased risk of childhood leukaemia (OR 2.6; 95% CI 1.03, 6.50). The risk increased with number of days being exposed during the last 6 months categorised in ”0”, ”1–30”, ”31–180” (p-value for trend=0.03). No excess risk of leukaemia was found for paternal exposure. Conclusion We found an excess risk of leukaemia in children having a mother reporting being exposed to benzene-containing ”gasoline or exhaust” prior to and/or during pregnancy.

Use of the general population as a reference might cause serious underestimation of the risk of cancer in working populations because of the healthy worker effect. Using incidence rates, we studied how this underestimation varied according to subtypes of cancer by comparing a large cohort of randomly selected Norwegian workers hired between 1981 and 2003 (n = 366,114) with the general Norwegian population. The cohort was linked to the Cancer Registry of Norway, including all new cancer cases (n= 11,271) reported up to 2003. We found marked potential for the healthy worker effect for overall cancer incidence in male workers (standardized incidence ratio (SIR) = 0.91, 95% confidence interval: 0.89, 0.93) but not in female workers (SIR = 0.99, 95% confidence interval: 0.95, 1.03). A statistically significantly lower incidence was found among men for cancers of the head and neck (SIR = 0.78), lung (SIR = 0.81), prostate (SIR = 0.93), kidney (SIR = 0.83), and bladder (SIR = 0.77) and for leukemia (SIR = 0.80), whereas an increased incidence was found for malignant melanoma among both men (SIR = 1.09) and women (SIR = 1.29) and for ovarian cancer in women (SIR = 1.32). Depending on the type of cancer being studied, marked potential exists for both underestimation and overestimation of cancer risk when the general population is used as the reference for studies of worker populations. cancer incidence; cohort studies; educational level; healthy worker effect; mortality

Objectives Characterize personal exposure to airborne hydrocarbons, particularly carcinogenic benzene, during spill of two different fresh crude oils at sea. Methods The study included 22 participants taking part in an «oil on water» field trial in the North Sea. Two types of fresh crude oils (light and heavy) were released six times over two consecutive days followed by different oil spill response methods. The participants were distributed on five boats; three open sampling boats (A, B, and C), one release ship (RS), and one oil recovery (OR) vessel. Assumed personal exposure was assessed a priori, assuming high exposure downwind and close to the oil slick (sampling boats), low exposure further downwind (100-200 m) and upwind from the oil slick (main deck of RS and OR vessel), and background exposure indoors (bridge of RS/OR vessel). Continuous measurements of total volatile organic compounds in isobutylene equivalents were performed with photoionization detectors placed in all five boats. Full-shift personal exposure to benzene, toluene, ethylbenzene, xylenes, naphthalene, and n-hexane was measured with passive thermal desorption tubes. Results Personal measurements of benzene, averaged over the respective sample duration, on Day 1 showed that participants in the sampling boats (A, B, and C) located downwind and close to the oil slick were highest exposed (0.14-0.59 ppm), followed by participants on the RS main deck (0.02-0.10 ppm) and on the bridge (0.004-0.03 ppm). On Day 2, participants in sampling boat A had high benzene exposure (0.87-1.52 ppm) compared to participants in sampling boat B (0.01-0.02 ppm), on the ships (0.06-0.10 ppm), and on the bridge (0.004-0.01 ppm). Overall, the participants in the sampling boats had the highest exposure to all of the compounds measured. The light crude oil yielded a five times higher concentration of total volatile organic compounds in air in the sampling boats (max 510 ppm) than the heavy crude oil (max 100 ppm) but rapidly declined to

Objectives This study is the first step in a larger study that aims to investigate the potential human exposure to hazardous hydrocarbons in air during oil spill combat offshore. The aim was to measure n-hexane, benzene, toluene, ethylbenzene, xylenes and naphthalene evaporated from fresh, light crude oils, and identify determinants significantly influencing the benzene evaporation. Methods A small scale open oil-on-water exposure system filled with seawater was used to produce a thin oil film ( Results Toluene, followed by benzene, ethylbenzene and n-hexane, yielded the highest air concentrations (6.0–11.3 ppm) of the measured VOCs, and declined rapidly with time. Xylenes and naphthalene yielded lower air concentrations (0.1–1.6 ppm) and did not show analogous decline during sampling. Benzene exceeded the short-term occupational exposure limit at both 2°C (3.5 ppm) and 13°C (4.6 ppm) the first 15 minutes of sampling. Benzene content in fresh oil, oil group (condensate/light oil) and wax content in fresh oil were significant determinants explaining 59–78% of the total variance in the outcome variables.

Background: Offshore workers in the Norwegian upstream petroleum industry are exposed to a number of chemicals such as organic solvents, mineral oils and other hydrocarbons, possibly contributing to an increased risk of multiple sclerosis (MS). Objective: To estimate the risk of MS in this population compared with the general working population in Norway, adjusting for education. Methods: Using the Norwegian Registry of Employers and Employees we included all 27,900 offshore workers registered from 1981 to 2003 and 366,805 referents from the general working population matched by gender, age and community of residence. The cohort was linked to the Norwegian MS Registry and the Norwegian Education Registry. Results: There was no increased risk of MS among the offshore workers. We found a marked and linear inverse relationship between level of education and the risk of MS in the total study population, with a rate ratio of 0.48 (95% CI, 0.53 to 0.88) for workers with a graduate degree compared to workers with elementary school only. Conclusions: These findings do not support a major aetiological role of petroleum-based products, but rather point to smoking and other lifestyle factors related to the level of education as being important for the risk of MS.

Benzene, an aromatic hydrocarbon that is a natural component of crude oil and natural gas, is toxic to the blood and blood-forming organs. Epidemiological studies have established an association between benzene exposure and acute myeloid leukemia, and increasing evidence also indicates a possible association between benzene and multiple myeloma. A specific benzene-associated myelodysplastic syndrome has also been suggested. Chronic hematotoxic effects of benzene exposure, including reduced lymphocyte, neutrophil and platelet counts in peripheral blood, have been detected at occupational exposure below a level that had previously been considered not to cause any health effects. Whether these abnormalities represent bone marrow damage and/or initial events in the development of a true neoplastic disease is not known. Together with a reported nonlinear relationship between benzene exposure and the level of various metabolites, favoring production of biologically reactive quinones at exposure below 1 part per million, these observations suggest that benzene even at low exposure levels may contribute to the risk of acute myeloid leukemia or myelodysplastic syndrome, especially among genetically susceptible individuals. publishedVersion

Benzene exposure has been shown to be related to acute myelogenous leukemia, while the association with multiple myeloma and non-Hodgkin lymphoma has been a much-debated issue. We performed a historical cohort study to investigate whether workers employed in Norway's upstream petroleum industry exposed to crude oil and other products containing benzene have an increased risk of developing various subtypes of hematologic neoplasms. Using the Norwegian Registry of Employers and Employees we included all 27,919 offshore workers registered from 1981 to 2003 and 366,114 referents from the general working population matched by gender, age, and community of residence. The cohort was linked to the Cancer Registry of Norway. Workers in the job category "upstream operator offshore", having the most extensive contact with crude oil, had an excess risk of hematologic neoplasms (blood and bone marrow) (rate ratio (RR) 1.90, 95% confidence interval (95% CI): 1.19-3.02). This was ascribed to an increased risk of acute myelogenous leukemia (RR 2.89, 95% CI: 1.25-6.67) and multiple myeloma (RR 2.49, 95% CI: 1.21-5.13). There were no statistical differences between the groups in respect to non-Hodgkin lymphoma. The results suggest that benzene exposure, which most probably caused the increased risk of acute myelogenous leukemia, also resulted in an increased risk of multiple myeloma.

Purpose: Characterize ethylbenzene and xylene air concentrations, and explore the biological exposure markers (urinary t,t-muconic acid (t,t-MA) and unmetabolized toluene) among petroleum workers offshore. Offshore workers have increased health risks due to simultaneous exposures to several hydrocarbons present in crude oil. We discuss the pooled benzene exposure results from our previous and current studies and possible co-exposure interactions. Methods: BTEX air concentrations were measured during three consecutive 12-h work shifts among 10 tank workers, 15 process operators, and 18 controls. Biological samples were collected pre-shift on the first day of study and post-shift on the third day of the study. Results: The geometric mean exposure over the three work shifts were 0.02ppm benzene, 0.05ppm toluene, 0.03ppm ethylbenzene, and 0.06ppm xylene. Benzene in air was significantly correlated with unmetabolized benzene in blood (r=0.69, p

Objectives To investigate cancer risk, particularly oesophageal cancer, among male upstream petroleum workers offshore potentially exposed to various carcinogenic agents. Methods Using the Norwegian Registry of Employers and Employees, 24765 male offshore workers registered from 1981 to 2003 was compared with 283002 male referents from the general working population matched by age and community of residence. The historical cohort was linked to the Cancer Registry of Norway and the Norwegian Cause of Death Registry. Results Male offshore workers had excess risk of oesophageal cancer (RR 2.6, 95% CI 1.4 to 4.8) compared with the reference population. Only the adenocarcinoma type had a significantly increased risk (RR 2.7, 95% CI 1.0 to 7.0), mainly because of an increased risk among upstream operators (RR 4.3, 95% CI 1.3 to 14.5). Upstream operators did not have significant excess of respiratory system or colon cancer or mortality from any other lifestyle-related diseases investigated. Conclusion We found a fourfold excess risk of oesophageal adenocarcinoma among male workers assumed to have had the most extensive contact with crude oil. Due to the small number of cases, and a lack of detailed data on occupational exposure and lifestyle factors associated with oesophageal adenocarcinoma, the results must be interpreted with caution. Nevertheless, given the low risk of lifestyle-related cancers and causes of death in this working group, the results add to the observations in other low-powered studies on oesophageal cancer, further suggesting that factors related to the petroleum stream or carcinogenic agents used in the production process might be associated with risk of oesophageal adenocarcinoma.

To compare differences in pre- and post-shift urinary 1-hydroxypyrene (1OHP) levels as a measure of internal dose of polycyclic aromatic hydrocarbons (PAHs) between two groups of oil production workers offshore assumed to be exposed to PAH, and to compare the exposed group to an unexposed control group. Participants’ (n = 42) urine samples, collected over a study period of three consecutive 12-h work days (pre-shift on the first day and post-shift on the third day), were analyzed using high performance liquid chromatography (HPLC) with fluorescence detection. Analysis of covariance was used in the statistical models. (1) Post-shift 1OHP levels were significantly higher in the exposed workers compared to the controls. (2) Tank workers and process operators did not show statistically significant different post-shift 1OHP levels. Altogether, this study indicates the presence of a low level PAH exposure among offshore oil production workers.

This study characterized the exposure of crude oil process operators to benzene and related aromatics during ordinary activity and investigated whether the operators take up benzene at this level of exposure. We performed the study on a fixed, integrated oil and gas production facility on Norway's continental shelf. The study population included 12 operators and 9 referents. We measured personal exposure to benzene, toluene, ethylbenzene and xylene during three consecutive 12-h work shifts using organic vapour passive dosimeter badges. We sampled blood and urine before departure to the production facility (pre-shift), immediately after the work shift on Day 13 of the work period (post-shift) and immediately before the following work shift (pre-next shift). We also measured the exposure to hydrocarbons during short-term tasks by active sampling using Tenax tubes. The arithmetic mean exposure over the 3 days was 0.042 ppm for benzene (range

We investigated associations between benzene exposure and alterations of proteins and cells of the immune system among workers maintaining cargo tanks containing crude oil residues. Individual exposure to benzene, benzene in blood and urine, peripheral blood lymphocytes (total lymphocytes, lymphocytes in subpopulations CD3, CD4, CD8, CD19, CD56 and CD4/CD8 ratio), complement factors C3 and C4 and serum concentration of immunoglobulins (IgG, IgA, IgM and IgE) were analysed among 13 tank workers and nine unexposed referents (catering section). Benzene exposure was measured during three consecutive 12-h work days. Blood and urine samples were collected pre-shift on the first day (baseline), post-shift on the third day, and pre-next shift on the following morning. The time spent in the cargo tank was logged. The individual geometric mean benzene exposure in the breathing zone of tank workers over 3 days was 0.15 p.p.m. (range 0.01-0.62 p.p.m.) (n = 26). The geometric mean benzene concentration in blood post-shift was 12.3 nmol/l among tank workers versus 0.7 nmol/l among the referents. Tank workers showed a decline (versus referents) in IgM from baseline to post-shift (t-test, P = 0.04) and IgA from baseline to pre-next shift (t-test, P = 0.01). They also showed a decline in CD4 T cells from baseline to post-shift (t-test, P = 0.04). Suppression correlated with benzene exposure, benzene concentrations in blood and urine and time spent in the tank. The groups did not differ significantly in the change in other immune parameters. The clinical significance is unknown and warrants further studies.