Ioannis Basinas

Endotoxin exposure and lung cancer risk: a systematic review and meta-analysis of the published literature on agriculture and cotton textile workers

ObjectiveTo examine the association between exposure to endotoxins and lung cancer risk by conducting a systematic review and meta-analysis of epidemiologic studies of workers in the cotton textile and agricultural industries; industries known for high exposure levels of endotoxins.MethodsRisk estimates were extracted from studies published before 2009 that met predefined quality criteria, including 8 cohort, 1 case–cohort, and 2 case–control studies of cotton textile industry workers, and 15 cohort and 2 case–control studies of agricultural workers. Summary risk estimates were calculated using random effects meta-analyses. Potential sources of heterogeneity were explored through subgroup analyses.ResultsThe summary risk of lung cancer was 0.72 (95% CI, 0.57–0.90) for textile workers and 0.62 (0.52–0.75) for agricultural workers. The relative risk of lung cancer was below 1.0 for most subgroups defined according to sex, study design, outcome, smoking adjustment, and geographic area. Two studies provided quantitative estimates of endotoxin exposure and both studies tended to support a dose–dependent protective effect of endotoxins on lung cancer risk.ConclusionDespite several limitations, this meta-analysis based on high-quality studies adds weight to the hypothesis that occupational exposure to endotoxin in cotton textile production and agriculture is protective against lung cancer.

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/m3 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. Endotoxins protective effects are most clearly observed among agricultural workers.

A comprehensive review of levels and determinants of personal exposure to dust and endotoxin in livestock farming

The respiratory health effects of livestock farming have been on debate for more than three decades. Endotoxin-contaminated organic dusts are considered as the most important respiratory hazards within livestock environments. A comprehensive review of the knowledge from studies assessing the exposure status of livestock farmers is still to be published. The present study reviews research published within the last 30 years on personal exposure of livestock farmers to organic dust and endotoxin, focusing on studies on pig, poultry and cattle farmers. Applied measurement methods and reported levels of personal exposure for the total, inhalable and respirable fractions are summarized and discussed, with emphasis on the intensity of exposure and the size and distribution of the reported exposure variability. In addition, available evidence on potential determinants of personal exposure to dust and endotoxin among these farmers are documented and discussed, taking results from exposure determinant studies using stationary sampling approaches into consideration. Research needs are addressed from an epidemiological and industrial hygiene perspective. Published studies have been heterogeneous in design, and applied methodologies and results were frequently inadequately reported. Despite these limitations and the presence of an enormous variability in personal exposure to dust and endotoxin, no clear downward trends in exposure with time were observed, suggesting that working environments within stables remains largely uncontrolled. Exposure control and prevention strategies for livestock farmers are urgently required. These should focus on the development of novel and improved methods of controlling dust and endotoxin exposure within stables based on the currently available knowledge on determinants of exposure.

Systematic Review of Respiratory Health Among Dairy Workers

ABSTRACT The dairy industry is changing on a global scale with larger, more efficient operations. The impact of this change on worker health and safety, specifically, associations between occupational lung disease and inhalation exposures, has yet to be reported in a comprehensive review of the scientific literature. Therefore, a three-tier process was used to identify information using a keyword search of online databases of scientific literature. Of the 147 citations reviewed, 52 met initial screening criteria, and 30 were included in this review. Dairy workers experience lung conditions such as asthma, chronic obstructive pulmonary disease, hypersensitivity pneumonitis, chronic bronchitis, and cancer. Recent pulmonary function studies have identified obstructive lung changes among dairy farm workers. The increased scale of dairy production with significant changes in technology and work practices has altered inhalation exposure patterns among dairy workers. The inhalation exposure in the dairy work environment may elicit differing inflammatory responses in relation to timing of initial exposure as well as to repeated exposures. Few studies have measured inhalation exposure while simultaneously assessing the impact of the exposure on lung function of dairy farm workers. Even fewer studies have been implemented to assess the impact of aerosol control technology to reduce inhalation exposure. Future research should evaluate worker exposure to aerosols through a task-based approach while utilizing novel methods to assess inhalation exposure and associated inflammatory responses. Finally, potential solutions should be developed and tested to reduce inhalation exposure to inflammatory agents and respiratory diseases in the dairy farm work environment.

The cohort of young Danish farmers - A longitudinal study of the health effects of farming exposure.

Working in agriculture poses a serious risk for development of respiratory diseases, especially when working in animal housing. Animal workers are exposed to a mixture of organic and inorganic dust together with fumes and gases, including allergens and microbial-associated molecular patterns with a potentially major impact on respiratory health and the immune system. Exposure to microbial agents in animal housing is associated with an increased prevalence of respiratory symptoms, including bronchial hyperresponsiveness, accelerated lung function decline, and neutrophil-mediated inflammation. These clinical findings are often seen without IgE-mediated sensitization. In fact it has been found in recent studies that the prevalence of atopic sensitization and atopic asthma is low among farmers compared with other populations. The SUS study was designed to identify the type and occurrence of respiratory symptoms and disease, and to investigate risk factors for respiratory disorders and changes in lung function among young farming students. The cohort of young Danish farmers was established in 1992/1994 and followed up in 2007/2008 with a participation rate of 51.7%. The cohort consists of 1734 male farming students, 230 female farming students, and 407 army recruits as controls.

Become a farmer and avoid new allergic sensitization: Adult farming exposures protect against new-onset atopic sensitization

cutoffs. Furthermore, although blood eosinophil levels are suggested to be useful biomarkers contributing to the characterization of subphenotypes of asthma, they poorly predict sputum eosinophil levels. Similarly, the more sensitive but less specific cutoff of 0.35 kU/L for atopy may result in children without active allergic inflammation to be classified as atopic. In addition, atopy may not be causally related to wheeze even if temporality is established, which is reflected in population-attributable risk proportions around 60%. Moreover, there is evidence that suggests that different sensitization patterns drive different phenotypes of wheeze or asthma and differential effects of eosinophil levels on asthma over time during childhood have been described. However, atopy and eosinophil levels were assessed only once and for atopy a limited number of allergens were tested, both precluding the exploration of sophisticated patterns. Likewise, because of the exclusion of children who had wheeze or asthma at baseline, analyses were restricted to late-onset wheeze, which has a stronger association with atopy than does early-onset persistent wheeze. Nonetheless, increased wheeze incidence in both atopic groups—low and high eosinophil levels—would not explain the discrepancy in the interaction measures between asthma at baseline and during follow-up. In conclusion, the detected synergistic interaction provides evidence that atopy and eosinophils act through a common causal pathway in the pathogenesis of childhood wheeze. Both biomarkers may be useful for predicting and phenotyping childhood wheeze in clinical routine, but special care should be devoted to patterns and levels of atopic sensitization and blood eosinophils.

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 levels, determinants and IgE mediated sensitization to bovine allergens among Danish farmers and non-farmers

BACKGROUND Bovine allergens can induce allergic airway diseases. High levels of allergens in dust from stables and homes of dairy farmers have been reported, but sparse knowledge about determinants for bovine allergen levels and associations between exposure level and sensitization is available. OBJECTIVE To investigate levels and determinants of bovine allergen exposure among dairy, pig and mink farmers (bedroom and stable), and among former and never farmers (bedroom), and to assess the prevalence of bovine allergen sensitization in these groups. METHODS In 2007-2008, 410 settled dust samples were collected in stables and in bedrooms using an electrostatic dust-fall collector over a 14 day period among 54 pig farmers, 27 dairy farmers, 3 mink farmers as well as 71 former and 48 never farmers in Denmark. For farmers sampling was carried out both during summer and winter. Bovine allergen levels (μg/m(2)) were measured using a sandwich ELISA. Determinants for bovine allergen exposure in stables and bedrooms were explored with mixed effect regression analyses. Skin prick test with bovine allergen was performed on 48 pig farmers, 20 dairy farmers, 54 former and 31 never farmers. RESULTS Bovine allergen levels varied by five orders of magnitude, as expected with substantially higher levels in stables than bedrooms, especially for dairy farmers. Bovine allergen levels in bedrooms were more than one order of magnitude higher for dairy farmers compared to pig farmers. Former and never farmers had low levels of bovine allergens in their bedroom. Bovine allergen levels during summer appeared to be somewhat higher than during winter. Increased bovine allergen levels in the bedroom were associated with being a farmer or living on a farm. Mechanical ventilation in the bedroom decreased bovine allergen level, significant for dairy farmers β=-1.4, p<0.04. No other significant effects of either sampling or residence characteristics were seen. Allergen levels in dairy stables were associated to type of dairy stable, but not to other stable or sampling characteristics. Sensitization to bovine allergens was only found in one pig farmer. CONCLUSION This study confirms high bovine allergen levels in dairy farms, but also suggests sensitization to bovine allergens among Danish farmers to be uncommon. Furthermore the importance of a carrier home effect on allergen load is emphasized. Whether the risk for bovine sensitization is related to the allergen level in the stable or the dwelling remains to be determined.

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.

Validation of Lower Tier Exposure Tools Used for REACH: Comparison of Tools Estimates With Available Exposure Measurements

Background Tier 1 exposure tools recommended for use under REACH are designed to easily identify situations that may pose a risk to health through conservative exposure predictions. However, no comprehensive evaluation of the performance of the lower tier tools has previously been carried out. The ETEAM project aimed to evaluate several lower tier exposure tools (ECETOC TRA, MEASE, and EMKG-EXPO-TOOL) as well as one higher tier tool (STOFFENMANAGER®). This paper describes the results of the external validation of tool estimates using measurement data. Methods Measurement data were collected from a range of providers, both in Europe and United States, together with contextual information. Individual measurement and aggregated measurement data were obtained. The contextual information was coded into the tools to obtain exposure estimates. Results were expressed as percentage of measurements exceeding the tool estimates and presented by exposure category (non-volatile liquid, volatile liquid, metal abrasion, metal processing, and powder handling). We also explored tool performance for different process activities as well as different scenario conditions and exposure levels. Results In total, results from nearly 4000 measurements were obtained, with the majority for the use of volatile liquids and powder handling. The comparisons of measurement results with tool estimates suggest that the tools are generally conservative. However, the tools were more conservative when estimating exposure from powder handling compared to volatile liquids and other exposure categories. In addition, results suggested that tool performance varies between process activities and scenario conditions. For example, tools were less conservative when estimating exposure during activities involving tabletting, compression, extrusion, pelletisation, granulation (common process activity PROC14) and transfer of substance or mixture (charging and discharging) at non-dedicated facilities (PROC8a; powder handling only). With the exception of STOFFENMANAGER® (for estimating exposure during powder handling), the tools were less conservative for scenarios with lower estimated exposure levels. Conclusions This is the most comprehensive evaluation of the performance of REACH exposure tools carried out to date. The results show that, although generally conservative, the tools may not always achieve the performance specified in the REACH guidance, i.e. using the 75th or 90th percentile of the exposure distribution for the risk characterisation. Ongoing development, adjustment, and recalibration of the tools with new measurement data are essential to ensure adequate characterisation and control of worker exposure to hazardous substances.