Risk of hypersensitivity pneumonitis and other interstitial lung diseases following organic dust exposure.

BACKGROUND: Organic dust is associated with hypersensitivity pneumonitis, and associations with other types of interstitial lung disease (ILD) have been suggested. We examined the association between occupational organic dust exposure and hypersensitivity pneumonitis and other ILDs in a cohort study. METHODS: The study population included all residents of Denmark born in 1956 or later with at least 1 year of gainful employment since 1976. Incident cases of hypersensitivity pneumonitis and other ILDs were identified in the Danish National Patient Register 1994-2015. Job exposure matrices were used to assign individual annual levels of exposure to organic dust, endotoxin and wood dust from 1976 to 2015. We analysed exposure-response relations by different exposure metrics using a discrete-time hazard model. RESULTS: For organic dust, we observed increasing risk with increasing cumulative exposure with incidence rate ratios (IRR) per 10 unit-years of 1.19 (95% CI 1.12 to 1.27) for hypersensitivity pneumonitis and 1.04 (95% CI 1.02 to 1.06) for other ILDs. We found increasing risk with increasing cumulative endotoxin exposure for hypersensitivity pneumonitis and other ILDs with IRRs per 5000 endotoxin units/m3-years of 1.55 (95% CI 1.38 to 1.73) and 1.09 (95% CI 1.00 to 1.19), respectively. For both exposures, risk also increased with increasing duration of exposure and recent exposure. No increased risks were observed for wood dust exposure. CONCLUSION: Exposure-response relations were observed between organic dust and endotoxin exposure and hypersensitivity pneumonitis and other ILDs, with lower risk estimates for the latter. The findings indicate that organic dust should be considered a possible cause of any ILD. TRIAL REGISTRATION NUMBER: j.no.: 1-16-02-196-17.

Factors influencing occupational exposure to pyrethroids and glyphosate: An analysis of urinary biomarkers in Malaysia, Uganda and the United Kingdom.

BACKGROUND: Long-term exposure to pesticides is often assessed using semi-quantitative models. To improve these models, a better understanding of how occupational factors determine exposure (e.g., as estimated by biomonitoring) would be valuable. METHODS: Urine samples were collected from pesticide applicators in Malaysia, Uganda, and the UK during mixing/application days (and also during non-application days in Uganda). Samples were collected pre- and post-activity on the same day and analysed for biomarkers of active ingredients (AIs), including synthetic pyrethroids (via the metabolite 3-phenoxybenzoic acid [3-PBA]) and glyphosate, as well as creatinine. We performed multilevel Tobit regression models for each study to assess the relationship between exposure modifying factors (e.g., mixing/application of AI, duration of activity, personal protective equipment [PPE]) and urinary biomarkers of exposure. RESULTS: From the Malaysia, Uganda, and UK studies, 81, 84, and 106 study participants provided 162, 384 and 212 urine samples, respectively. Pyrethroid use on the sampling day was most common in Malaysia (n = 38; 47%), and glyphosate use was most prevalent in the UK (n = 93; 88%). Median pre- and post-activity 3-PBA concentrations were similar, with higher median concentrations post-compared to pre-activity for glyphosate samples in the UK (1.7 to 0.5 µg/L) and Uganda (7.6 to 0.8 µg/L) (glyphosate was not used in the Malaysia study). There was evidence from individual studies that higher urinary biomarker concentrations were associated with mixing/application of the AI on the day of urine sampling, longer duration of mixing/application, lower PPE protection, and less education/literacy, but no factor was consistently associated with exposure across biomarkers in the three studies. CONCLUSIONS: Our results suggest a need for AI-specific interpretation of exposure modifying factors as the relevance of exposure routes, levels of detection, and farming systems/practices may be very context and AI-specific.

Impact of occupational pesticide exposure assessment method on risk estimates for prostate cancer, non-Hodgkin's lymphoma and Parkinson's disease: results of three meta-analyses.

Assessment of occupational pesticide exposure in epidemiological studies of chronic diseases is challenging. Biomonitoring of current pesticide levels might not correlate with past exposure relevant to disease aetiology, and indirect methods often rely on workers' imperfect recall of exposures, or job titles. We investigated how the applied exposure assessment method influenced risk estimates for some chronic diseases. In three meta-analyses the influence of exposure assessment method type on the summary risk ratio (sRR) of prostate cancer (PC) (25 articles), non-Hodgkin's lymphoma (NHL) (29 articles) and Parkinson's disease (PD) (32 articles) was investigated. Exposure assessment method types analysed were: group-level assessments (eg, job titles), self-reported exposures, expert-level assessments (eg, job-exposure matrices) and biomonitoring (eg, blood, urine). Additionally, sRRs were estimated by study design, publication year period and geographic location where the study was conducted. Exposure assessment method types were not associated with statistically significant different sRRs across any of the health outcomes. Heterogeneity in results varied from high in cancer studies to moderate and low in PD studies. Overall, case-control designs showed significantly higher sRR estimates than prospective cohort designs. Later NHL publications showed significantly higher sRR estimates than earlier. For PC, studies from North America showed significantly higher sRR estimates than studies from Europe. We conclude that exposure assessment method applied in studies of occupational exposure to pesticides appears not to have a significant effect on risk estimates for PC, NHL and PD. In systematic reviews of chronic health effects of occupational exposure to pesticides, epidemiological study design, publication year and geographic location, should primarily be considered.

Systematic review of methods used to assess exposure to pesticides in occupational epidemiology studies, 1993-2017.

OBJECTIVE: Numerous exposure assessment methods (EAM) exist for investigating health effects of occupational exposure to pesticides. Direct (eg, biomonitoring) and indirect methods (eg, self-reported exposures) are however associated with degrees of exposure misclassification. We systematically reviewed EAM in studies of occupational pesticide exposure. METHODS: We searched for articles reporting observational epidemiological studies in MEDLINE and Embase published 1993 to 2017. The relative frequency of EAM was analysed according to EAM type (direct and indirect methods), health outcome, study design, study location (country) and specificity of assessment. Temporal trends in EAM were analysed. RESULTS: In 1298 included articles 1521 EAM occurrences were documented. Indirect EAM (78.3%), primarily self-reported exposures (39.3%) and job titles assessments (9.5%), were mainly applied in case-control studies (95.0%), in high-income countries (85.0%) and in studies of doctor-diagnosed health outcomes (>85%). Direct EAM (20.8%), primarily biomonitoring of blood (15.6%) or urine (4.7%), were predominantly applied in cross-sectional studies (29.8%), in lower middle-income countries (40.9%) and in studies of neurological (50.0%) outcomes. Between 1993 to 2017 no distinct time trends regarding the ratio indirect to direct methods was seen. Within the category of indirect methods use of self-reported exposures and job exposure matrices increased while assessments by job titles and registers decreased. The use of algorithms showed no trend. The specificity of pesticide assessment increased since studies assessing exposure by using job title as a proxy declined. Assessments of type of pesticide increased. CONCLUSION: Over the last 25 years, the ratio (5:1) of indirect to direct EAM applied in articles on occupational pesticide epidemiology stayed relatively constant; changes were mainly attributable to increasing use of self-reported exposures and job exposure matrices. This review, combined with studies assessing EAM validity, will inform on magnitudes of exposure misclassification and help improve the quality of studies on occupational pesticides exposure.

A nationwide follow-up study of occupational organic dust exposure and risk of chronic obstructive pulmonary disease (COPD).

OBJECTIVES: To study exposure-response relations between cumulative organic dust exposure and incident chronic obstructive pulmonary disease (COPD) among subjects employed in the Danish farming and wood industry. METHODS: We studied exposure-response relations between cumulative organic dust exposure and incident COPD (1997-2013) among individuals born during 1950-1977 in Denmark ever employed in the farming or wood industry (n=1 75 409). Industry-specific employment history (1964-2007), combined with time-dependent farming and wood industry-specific exposure matrices defined cumulative exposure. We used logistic regression analysis with discrete survival function adjusting for age, sex and calendar year. Adjustment for smoking status was explored in a subgroup of 4023 with smoking information available. RESULTS: Cumulative organic dust exposure was inversely associated with COPD (adjusted rate ratios (RRadj (95% CIs) of 0.90 (0.82 to 0.99), 0.76 (0.69 to 0.84) and 0.52 (0.47 to 0.58) for intermediate-low, intermediate-high and high exposure quartiles, respectively, compared with the lowest exposure quartile). Lagging exposure 10 years was not consistently suggestive of an association between cumulative exposure and COPD; RRadj (95% CI): 1.05 (0.94 to 1.16), 0.92 (0.83 to 1.02) and 0.63 (0.56 to 0.70). Additional stratification by duration of employment showed no clear association between organic dust exposure and COPD except for the longer exposed (15-40 years) where an inverse association was indicated. Subgroup analyses showed that smoking had no impact on exposure-response estimates. CONCLUSIONS: Our findings show no increased risk of COPD with increasing occupational exposure to organic dust in the farming or wood industry. Potential residual confounding by smoking can, however, not be ruled out.

High exposure to endotoxin in farming is associated with less new-onset pollen sensitisation.

OBJECTIVES: Little is known about risk factors for new onset and loss of atopic sensitisation in adulthood. The aim is to examine the longitudinal effect of quantitatively assessed endotoxin exposures on changes in specific allergen sensitisation in young adults. METHODS: The cohort consisted of 1113 young Danish farmers and rural controls, with a mean age of 19 years at baseline. Sensitisation to birch pollen, grass pollen, cat dander and house dust mite was measured by specific IgE levels in serum samples from baseline and at 15 years' follow-up. Changes in sensitisation were analysed in relation to cumulative endotoxin exposure during follow-up, considering early life farm exposure. RESULTS: Endotoxin exposure during follow-up was significantly associated with less new onset of specifically grass and birch pollen sensitisation. For the highest versus lowest quartile of cumulative endotoxin exposure, the OR for new-onset IgE sensitisation was 0.35 (0.13-0.91) for birch and 0.14 (0.05-0.50) for grass. On the other hand, loss of pollen sensitisation showed a positive, although mostly non-significant, association with increased levels of endotoxin exposure. Endotoxin exposure was not associated with significant changes in cat dander and house dust mite sensitisation. CONCLUSIONS: High exposure to endotoxin during young adulthood appears to protect against new onset of pollen sensitisation, independent of childhood farm exposure.

Feedback on Measured Dust Concentrations Reduces Exposure Levels Among Farmers.

BACKGROUND: The high burden of exposure to organic dust among livestock farmers warrants the establishment of effective preventive and exposure control strategies for these workers. The number of intervention studies exploring the effectiveness of exposure reduction strategies through the use of objective measurements has been limited. OBJECTIVE: To examine whether dust exposure can be reduced by providing feedback to the farmers concerning measurements of the exposure to dust in their farm. METHODS: The personal dust levels of farmers in 54 pig and 26 dairy cattle farms were evaluated in two measurement series performed approximately 6 months apart. Detailed information on work tasks and farm characteristics during the measurements were registered. Participating farms were randomized a priori to a control (n = 40) and an intervention group (n = 40). Shortly after the first visit, owners of intervention farms only received a letter with information on the measured dust concentrations in the farm together with some general advises on exposure reduction strategies (e.g. use of respirators during certain tasks). Relationships between measured dust concentrations and intervention status were quantified by means of linear mixed effect analysis with farm and worker id as random effects. Season, type of farming, and work tasks were treated as fixed effects. Changes in exposure over time were explored primarily at a farm level in models combined, as well as separate for pig and cattle farmers. RESULTS: After adjustment for fixed effects, an overall reduction of 23% in personal dust exposures was estimated as a result of the intervention (P = 0.02). Exposure reductions attributable to the intervention were similar across pig and cattle farmers, but statistically significant only for pig farmers. Intervention effects among pig farmers did not depend on the individuals' information status; but among cattle farmers a significant 48% reduction in exposure was found only among individuals that reported to have been informed. No systematic differences in changes over time considering the use of respiratory protection between the intervention and control groups were observed. CONCLUSION: The results of the present study suggest reductions between 20 and 30% in personal exposure to inhalable dust to be feasible through simple information provided to the farm owners regarding actual levels of exposure together with instructions on basic measures of prevention. The exact reasons for these effects are unclear, but likely they involve changes in behavior and working practices among intervention farmers.

The effect of occupational farming on lung function development in young adults: a 15-year follow-up study.

OBJECTIVES: Longitudinal studies on the effect of farming on lung function in young participants are few. Our objective was to explore if exposure to farming impaired lung function in young adults. METHODS: We studied 1964 farming students and 407 controls in 1992/2004, and carried out follow-up in 2007/2008. Spirometry, skin prick test and bronchial hyper-responsiveness (BHR) were assessed, height and weight measured, and questionnaires covering health and occupation were collected. Cumulative dust and endotoxin exposures were estimated from modelled personal dust measurements. Lung function effect was expressed as change in z-score during follow-up using the Global Lung Initiative 2012 project prediction equations. Longitudinal data were available for 1134 young participants ≤25 years at baseline. RESULTS: We found no differences in lung function Δz-scores between farmers and controls, however, adjusted multivariable linear regression showed a negative effect among current farmers on ΔzFEV1 (forced expiratory volume in 1 s; -0.12, p=0.006) and ΔzFEV1/FVC (forced vital capacity; -0.15, p=0.009) compared to ex-farmers. An interaction was found between sex and farming, showing that current farming suppresses ΔzFEV1 and ΔzFVC more among females. Smoking in farmers had a deleterious effect on ΔzFEV1, which was not seen in controls, though no significant interaction was found. Farm upbringing protected against impairment of lung function, and BHR at baseline had a deleterious effect on ΔzFEV1 only in those not raised on a farm. CONCLUSIONS: We conclude that being a current farmer is associated with a negative effect on lung function, when compared to ex-farmers, with females being more susceptible. Being raised on a farm protects against the adverse effect of BHR on change in lung function.

Dust, endotoxin, fungi, and bacteria exposure as determined by work task, season, and type of plant in a flower greenhouse.

BACKGROUND: Greenhouse workers are exposed to dust, endotoxin, fungi, and bacteria potentially causing airway inflammation as well as systemic symptoms. Knowledge about determinants of exposure is a prerequisite for efficient prevention through knowledge-based reduction in exposure. The objective of this study was to assess the occupational exposure in a flower greenhouse and to investigate the impact of work tasks on the intensity and variability in exposure. METHODS: Seventy-six personal full-shift exposure measurements were performed on 38 employees in a Danish flower greenhouse producing Campanula, Lavandula, Rhipsalideae, and Helleborus. The samples were gravimetrically analysed for inhalable dust. Endotoxin was assessed by the Limulus Amoebocyte Lysate test and culture-based quantification of bacteria and fungi was performed. Information on the performed tasks during sampling was extracted from the greenhouse electronic task logging system. Associations between log-transformed exposure outcomes, season, and work tasks were examined in linear mixed-effects regression with worker identity as random effect. RESULTS: Measured concentrations ranged between 0.04 and 2.41mg m(-3) for inhalable dust and between 0.84 and 1097 EU m(-3) for endotoxin exposure, with the highest mean levels measured during Lavandula and Campanula handling, respectively. Personal exposure to fungi ranged between 1.8×10(2) and 3.4×10(6) colony-forming units (CFU) m(-3) and to bacteria between 1.6×10(1) and 4.2×10(5) CFU m(-3). Exposure to dust, endotoxin, fungi, and bacteria differed between seasons. Packing Lavandula, sticking, potting, and grading Rhipsalideae, and all examined tasks related to Campanula production except sticking increased dust exposure. Endotoxin exposure was increased during sticking Campanula and pinching or packing Rhipsalideae, and fungi exposure was elevated by subtasks performed in the research and development area for Campanula, and by potting, packing/dumping Campanula. Sticking and working with subtasks in the research and development area for Campanula increased bacteria exposure. CONCLUSION: This study revealed moderate dust exposure levels compared to the levels observed in other greenhouse productions and other occupations with organic dust exposure such as farming. However, high exposures to bacteria and fungi were detected during selected tasks and the proposed health-based endotoxin exposure limit of 90 EU m(-3) was exceeded in 30% of the samples, which may have health implications for the employees. Exposure levels were found to vary depending on the tasks performed, and thereby results can be used to direct task-based initiatives to reduce workplace exposures.

Exposure-affecting factors of dairy farmers' exposure to inhalable dust and endotoxin.

INTRODUCTION: Studies on determinants of dairy farmers' exposure to dust and endotoxin have been sparse and so far none has addressed the combined effect of tasks and farm characteristics. OBJECTIVE: To study whether and how work tasks and specific stable characteristics influence the level of dairy farmers' personal exposure to inhalable dust and endotoxin. METHODS: We applied an observational design involving full-shift repeated personal measurements of inhalable dust and endotoxin exposure among 77 subjects (owners and farm workers) from 26 dairy farms. Performed tasks were self-registered in activity diaries, and information on stable characteristics was collected through personal interviews and walk-through surveys. Associations between exposure, tasks, and stable characteristics were examined in linear mixed-effect models with individual and farm treated as random effects. Separate as well as combined models for tasks and stable characteristics were elaborated. RESULTS: The 124 personal samples collected had a geometric mean level (geometric standard deviation) of 360 EU m(-3) (3.8) for endotoxin exposure and of 1.0mg m(-3) (2.7) for dust exposure. Identified factors that increased endotoxin exposure included a lower outdoor temperature and use of slope-based or back-flushed slurry systems along with milking, distribution of bedding, and handling of feed and seeds in barns. For dust, exposure was higher when fully automatic (robotic) milking was used and during re-penning of animals, handling of feed and seeds, handling of silos and when distributing bedding. Dust exposure increased also as a result of use of rail feed dispensers in a model without fully automatic milking. CONCLUSIONS: The current exposure to dust and in particular endotoxin among Danish dairy farmers demand effective strategies to reduce their exposure. The present findings suggest that future interventions should focus on feeding and manure handling systems. Use of respirators during handling of feed and distribution of bedding should be advised until adequate risk management measures have been established. The expected increased use of fully automatic milking in the future might increase dust exposure of dairy farmers.

Occupational exposure to pesticides and neurobehavioral outcomes. Impact of different original and recalled exposure measures on the associations.

BACKGROUND: Several measures of occupational exposure to pesticides have been used to study associations between exposure to pesticides and neurobehavioral outcomes. This study assessed the impact of different exposure measures for glyphosate and mancozeb on the association with neurobehavioral outcomes based on original and recalled self-reported data with 246 smallholder farmers in Uganda. METHODS: The association between the 6 exposure measures and 6 selected neurobehavioral test scores was investigated using linear multivariable regression models. Exposure measures included original exposure measures for the previous year in 2017: (i) application status (yes/no), (ii) number of application days, (iii) average exposure-intensity scores (EIS) of an application and (iv) number of EIS-weighted application days. Two additional measures were collected in 2019: (v) recalled application status and (vi) recalled EIS for the respective periods in 2017. RESULTS: Recalled applicator status and EIS were between 1.2 and 1.4 times more frequent and higher for both pesticides than the original application status and EIS. Adverse associations between the different original measures of exposure to glyphosate and 4 neurobehavioral tests were observed. Glyphosate exposure based on recalled information and all mancozeb exposure measures were not associated with the neurobehavioral outcomes. CONCLUSIONS: The relation between the different original self-reported glyphosate exposure measures and neurobehavioral test scores appeared to be robust. When based on recalled exposure measures, associations observed with the original exposure measures were no longer present. Therefore, future epidemiological studies on self-reported exposure should critically evaluate the potential bias towards the null in observed exposure-response associations.

Exposure to inhalable dust and endotoxin among Danish pig farmers affected by work tasks and stable characteristics.

OBJECTIVE: To identify working tasks and stable characteristics that determine intensity and variability of personal exposure to dust and endotoxin among pig farmers. METHODS: Three hundred fifty-four personal full-shift measurements were performed in 231 farmers employed in 53 Danish pig farms. Filters were gravimetrically analysed for inhalable dust and for endotoxin by the Limulus amebocyte lysate assay. Information on working tasks and stable characteristics were collected using self-reported activity diaries and walk-through surveys performed in conjunction with the measurements. Associations between log-transformed dust and endotoxin exposure and working tasks and stable characteristics were examined using linear mixed-effects analysis. In these models, worker and farm identity were treated as random effects and working tasks and stable characteristics as fixed effects. Both separate and combined models for tasks and stable characteristics were elaborated. RESULTS: Inhalable dust concentrations ranged between 0.1 and 48 mg m(-3) and endotoxin concentrations varied between 9.2 and 370,000 EU m(-3). Field work activities played a dominant role on the exposure variability. Indoor working tasks with intense animal activity or handling of feed materials increased exposure concentrations, whereas engagement in field work was associated with lower exposure concentrations. High-pressure water cleaning increased endotoxin exposure but did not affect exposure to inhalable dust. Stable characteristics related to feeding practices and type of ventilation were determinants of exposure to inhalable dust. For endotoxin, the most important determinants were use of dry feed and slatted floor coverage. Feeding practices solely explained all between-farms variability in exposure to inhalable dust and endotoxin. CONCLUSIONS: These findings suggest feeding systems, flooring and ventilation to be potential areas where improved methods can reduce exposure to dust and endotoxin among pig farmers. Further, they highlight particular tasks involving feeding and intense animal handling as sources of very high levels of exposure. The pig farming industry is encouraged to focus on exposure reduction. Use of respirators during performance of working tasks where levels of exposure are particularly high ought to be considered until adequate hygienic solutions have been established.

Exposure assessment for repeated sub-concussive head impacts in soccer: The HEalth and Ageing Data IN the Game of football (HEADING) study.

The purpose of this paper was to develop exposure estimates for repetitive sub-concussive head impacts (RSHI) for use in epidemiological analyses. We used a questionnaire to collect lifetime history of heading and other head contacts associated with training and playing football from 159 former footballers all members of the English professional football association. We used linear mixed effect regression with player as the random effect, to model the number of headers, blows to the head and head-to-head impacts as a function of potential exposure affecting factors, which were treated as the fixed effects. Exposure affecting factors included playing position, league, context of play (game vs training) and decade of play. Age at time of response to the questionnaire was also included in the models. In model results, playing position was important, with RSHIs being highest among defenders and lowest among goalkeepers. Players headed the ball more during games than in training, and when playing in amateur or youth leagues compared with semi-professional or professional leagues. The average number of reported head impacts declined linearly throughout the observation period (1949-2015). The derived final model for headers explained 43%, 9% and 36% of the between player, within player and total variance in exposure, respectively with good precision and predictive performance. These findings are generally in agreement with previously published results pointing towards the models forming a valid method for estimating exposure to RSHI among former footballers although some further external validation is still warranted.

Validation of a COVID-19 Job Exposure Matrix (COVID-19-JEM) for Occupational Risk of a SARS-CoV-2 Infection at Work: Using Data of Dutch Workers.

OBJECTIVES: A COVID-19 Job Exposure Matrix (COVID-19-JEM) has been developed, consisting of four dimensions on transmission, two on mitigation measures, and two on precarious work. This study aims to validate the COVID-19-JEM by (i) comparing risk scores assigned by the COVID-19-JEM with self-reported data, and (ii) estimating the associations between the COVID-19-JEM risk scores and self-reported COVID-19. METHODS: Data from measurements 2 (July 2020, n = 7690) and 4 (March 2021, n = 6794) of the Netherlands Working Conditions Survey-COVID-19 (NWCS-COVID-19) cohort study were used. Responses to questions related to the transmission risks and mitigation measures of Measurement 2 were used to calculate self-reported risk scores. These scores were compared with the COVID-19-JEM attributed risk scores, by assessing the percentage agreement and weighted kappa (κ). Based on Measurement 4, logistic regression analyses were conducted to estimate the associations between all COVID-19-JEM risk scores and self-reported COVID-19 (infection in general and infected at work). RESULTS: The agreement between the COVID-19-JEM and questionnaire-based risk scores was good (κ ≥ 0.70) for most dimensions, except work location (κ = 0.56), and face covering (κ = 0.41). Apart from the precarious work dimensions, higher COVID-19-JEM assigned risk scores had higher odds ratios (ORs; ranging between 1.28 and 1.80) on having had COVID-19. Associations were stronger when the infection were thought to have happened at work (ORs between 2.33 and 11.62). CONCLUSIONS: Generally, the COVID-19-JEM showed a good agreement with self-reported infection risks and infection rates at work. The next step is to validate the COVID-19-JEM with objective data in the Netherlands and beyond.

Exploring the relationship between job characteristics and infection: Application of a COVID-19 job exposure matrix to SARS-CoV-2 infection data in the United Kingdom.

OBJECTIVE: This study aimed to assess whether workplace exposures as estimated via a COVID-19 job exposure matrix (JEM) are associated with SARS-CoV-2 in the UK. METHODS: Data on 244 470 participants were available from the Office for National Statistics Coronavirus Infection Survey (CIS) and 16 801 participants from the Virus Watch Cohort, restricted to workers aged 20-64 years. Analysis used logistic regression models with SARS-CoV-2 as the dependent variable for eight individual JEM domains (number of workers, nature of contacts, contact via surfaces, indoor or outdoor location, ability to social distance, use of face covering, job insecurity, and migrant workers) with adjustment for age, sex, ethnicity, index of multiple deprivation (IMD), region, household size, urban versus rural area, and health conditions. Analyses were repeated for three time periods (i) February 2020 (Virus Watch)/April 2020 (CIS) to May 2021), (ii) June 2021 to November 2021, and (iii) December 2021 to January 2022. RESULTS: Overall, higher risk classifications for the first six domains tended to be associated with an increased risk of infection, with little evidence of a relationship for domains relating to proportion of workers with job insecurity or migrant workers. By time there was a clear exposure-response relationship for these domains in the first period only. Results were largely consistent across the two UK cohorts. CONCLUSIONS: An exposure-response relationship exists in the early phase of the COVID-19 pandemic for number of contacts, nature of contacts, contacts via surfaces, indoor or outdoor location, ability to social distance and use of face coverings. These associations appear to have diminished over time.

Development of a quantitative North and Central European job exposure matrix for wood dust.

Wood dust is an established carcinogen also linked to several non malignant respiratory disorders. A major limitation in research on wood dust and its health effects is the lack of (historical) quantitative estimates of occupational exposure for use in general population-based case-control or cohort studies. The present study aimed to develop a multinational quantitative Job Exposure Matrix (JEM) for wood dust exposure using exposure data from several Northern and Central European countries. For this, an occupational exposure database containing 12653 personal wood dust measurements collected between 1978 and 2007 in Denmark, Finland, France, The Netherlands, Norway, and the United Kingdom (UK) was established. Measurement data were adjusted for differences in inhalable dust sampling efficiency resulting from the use of different dust samplers and analysed using linear mixed effect regression with job codes (ISCO-88) and country treated as random effects. Fixed effects were the year of measurement, the expert assessment of exposure intensity (no, low, and high exposure) for every ISCO-88 job code from an existing wood dust JEM and sampling duration. The results of the models suggest that wood dust exposure has declined annually by approximately 8%. Substantial differences in exposure levels between countries were observed with the highest levels in the United Kingdom and the lowest in Denmark and Norway, albeit with similar job rankings across countries. The jobs with the highest predicted exposure are floor layers and tile setters, wood-products machine operators, and building construction labourers with geometric mean levels for the year 1997 between 1.7 and 1.9 mg/m3. The predicted exposure estimates by the model are compared with the results of wood dust measurement data reported in the literature. The model predicted estimates for full-shift exposures were used to develop a time-dependent quantitative JEM for exposure to wood dust that can be used to estimate exposure for participants of general population studies in Northern European countries on the health effects from occupational exposure to wood dust.

Self-reported and urinary biomarker-based measures of exposure to glyphosate and mancozeb and sleep problems among smallholder farmers in Uganda.

OBJECTIVE: We aim to showcase the impact of applying eight different self-reported and urinary biomarker-based exposure measures for glyphosate and mancozeb on the association with sleep problems in a study among 253 smallholder farmers in Uganda. METHODS: The questionnaire-based exposure measures included: (1) the number of application days of any pesticide in the last 7 days (never, 1-2; >2 days) and six glyphosate and mancozeb-specific measures: (2) application status over the last 12 months (yes/no), (3) recent application status (never, last 7 days and last 12 months), (4) the number of application days last 12 months, (5) average exposure-intensity scores (EIS) and (6) EIS-weighted number of application days in last 12 months. Based on 384 repeated urinary biomarker concentrations of ethylene thiourea (ETU) and glyphosate from 84 farmers, we also estimated (7) average biomarker concentrations for all 253 farmers. Also in the 84 farmers the measured pre-work and post-work biomarker concentrations were used (8). Multivariable logistic regression models were used to assess the association between the exposure measures and selected Medical Outcomes Study Sleep Scale (MOS-SS) indices (6-item, sleep inadequacy and snoring). RESULTS: We observed positive associations between (1) any pesticide application in the last 7 days with all three MOS-SS indices. Glyphosate application in the last 7 days (3) and mancozeb application in the last 12 months (3) were associated with the 6-item sleep problem index. The estimated average urinary glyphosate concentrations showed an exposure-response association with the 6-item sleep problem index and sleep inadequacy in the same direction as based on self-reported glyphosate application in the last 7 days. In the analysis with the subset of 84 farmers, both measured and modelled post-work urinary glyphosate concentration showed an association with snoring. CONCLUSIONS: Self-reported, estimated average biomarker concentrations and measured urinary biomarker exposure measures of glyphosate and mancozeb showed similar exposure-response associations with sleep outcomes.

Associations between an international COVID-19 job exposure matrix and SARS-CoV-2 infection among 2 million workers in Denmark.

OBJECTIVES: This study investigates the associations between the Danish version of a job exposure matrix for COVID-19 (COVID-19-JEM) and Danish register-based SARS-CoV-2 infection information across three waves of the pandemic. The COVID-19-JEM consists of four dimensions on transmission: two on mitigation measures, and two on precarious work characteristics. METHODS: The study comprised 2 021 309 persons from the Danish working population between 26 February 2020 and 15 December 2021. Logistic regression models were applied to assess the associations between the JEM dimensions and overall score and SARS-CoV-2 infection across three infection waves, with peaks in March-April 2020, December-January 2021, and February-March 2022. Sex, age, household income, country of birth, wave, residential region and during wave 3 vaccination status were accounted for. RESULTS: Higher risk scores within the transmission and mitigation dimensions and the overall JEM score resulted in higher odds ratios (OR) of a SARS-CoV-2 infection. OR attenuated across the three waves with ranges of 1.08-5.09 in wave 1, 1.06-1.60 in wave 2, and 1.05-1.45 in those not (fully) vaccinated in wave 3. In wave 3, no associations were found for those fully vaccinated. In all waves, the two precarious work dimensions showed weaker or inversed associations. CONCLUSIONS: The COVID-19-JEM is a promising tool for assessing occupational exposure to SARS-CoV-2 and other airborne infectious agents that mainly spread between people who are in close contact with each other. However, its usefulness depends on applied restrictions and the vaccination status in the population of interest.

Sensitisation to common allergens and respiratory symptoms in endotoxin exposed workers: a pooled analysis.

OBJECTIVE: To test the hypotheses that current endotoxin exposure is inversely associated with allergic sensitisation and positively associated with non-allergic respiratory diseases in four occupationally exposed populations using a standardised analytical approach. METHODS: Data were pooled from four epidemiological studies including 3883 Dutch and Danish employees in veterinary medicine, agriculture and power plants using biofuel. Endotoxin exposure was estimated by quantitative job-exposure matrices specific for the study populations. Dose-response relationships between exposure, IgE-mediated sensitisation to common allergens and self-reported health symptoms were assessed using logistic regression and generalised additive modelling. Adjustments were made for study, age, sex, atopic predisposition, smoking habit and farm childhood. Heterogeneity was assessed by analysis stratified by study. RESULTS: Current endotoxin exposure was dose-dependently associated with a reduced prevalence of allergic sensitisation (ORs of 0.92, 0.81 and 0.66 for low mediate, high mediate and high exposure) and hay fever (ORs of 1.16, 0.81 and 0.58). Endotoxin exposure was a risk factor for organic dust toxic syndrome, and levels above 100 EU/m(3) significantly increased the risk of chronic bronchitis (p<0.0001). Stratification by farm childhood showed no effect modification except for allergic sensitisation. Only among workers without a farm childhood, endotoxin exposure was inversely associated with allergic sensitisation. Heterogeneity was primarily present for biofuel workers. CONCLUSIONS: Occupational endotoxin exposure has a protective effect on allergic sensitisation and hay fever but increases the risk for organic dust toxic syndrome and chronic bronchitis. Endotoxin's protective effects are most clearly observed among agricultural workers.