Assessing the health impact of interventions for baker's allergy and asthma in supermarket bakeries: a group randomised trial.

PURPOSE: To assess the impact of an intervention for baker's allergy and asthma in supermarket bakeries. METHODS: A group randomised trial conducted in 31 bakeries (n = 337 bakers) that were randomly assigned to one of two intervention groups (n = 244 bakers) and a control group (n = 93 bakers). Health data collected prior to and 1-year after the intervention included information obtained from an ECRHS questionnaire; tests for atopy and serum-specific IgE to cereal flours; fractional exhaled nitric oxide (FeNO). Data from the two intervention groups were combined to form one intervention group for purposes of the statistical analysis. RESULTS: At 1 year of follow-up, the incidence and level of decline of work-related ocular-nasal and chest symptoms, sensitisation status and elevated FeNO (FeNO > 25 ppb) was similar in both intervention and control groups. The mean FeNO difference was also similar across both groups (2.2 ppb vs 1.7 ppb, p = 0.86). In those with FeNO > 25 ppb at baseline, the decline was greater in the intervention compared to control group (16.9 ppb vs 7.7 ppb, p = 0.24). Multivariate logistic regression models (adjusting for smoking, baseline sensitisation to cereal flour, baseline FeNO > 25 ppb) did not demonstrate an appreciable FeNO decline (≥ 10%) in the intervention compared to control group. However, stratification by the presence of work-related ocular-nasal symptoms in bakers at baseline demonstrated a significant FeNO decline (≥ 10%) in the intervention compared to the control group (OR 3.73, CI 1.22-11.42). CONCLUSION: This study demonstrates some evidence of an intervention effect on FeNO 1 year after an intervention, particularly in bakers with work-related ocular-nasal symptoms.

Environmental Pollution as a Risk Factor in Testicular Tumour Development: Focus on the Interaction between Bisphenol A and the Associated Immune Response.

Bisphenol A (BPA) is an endocrine disruptor to which animals and humans are highly exposed. Many reports have established a relationship between BPA exposure and breast cancer incidence, especially during critical periods of development. However, its effects on the immune response in testicular tumour growth have not yet been described. Thus, we wanted to analyse the effect of perinatal BPA exposure in pregnant female mice and the immune response modulation and tumour growth in an intratesticular cancer model in offspring male mice. Pregnant female mice were exposed to a dose of 250 mg/kg/day/body weight of BPA in their drinking water. In adulthood, male offspring underwent intrascrotal inoculation with 4T1 cancer cells. On day 21 after inoculation, mice were euthanised, and serum was obtained to measure BPA levels using HPLC coupled to mass spectrometry. The percentages of immune cell populations in peripheral lymph nodes (PLN), the spleen and tumours were evaluated by flow cytometry. In addition, the tumour expression of IL-10, TNF-α and TGF-ß was analysed by RT-PCR. Of note, we found detectable circulating levels of BPA in the offspring of mothers exposed to it while pregnant. Remarkably, BPA treatment promoted tumour growth by about 75% compared to mice coming from female mice that did not receive the compound. Perinatal exposure to BPA modulated the percentages of different immune cells in the spleen and PLN. In addition, the expression of inflammatory-related cytokines (IL-10 and TNF-α) in the tumours was significantly enhanced compared to control and vehicle groups. In conclusion, the perinatal BPA administration in pregnant female mice modulated different cellular and molecular immune components that resulted in outstanding testicular tumour size in male offspring.

Update on metal-induced occupational lung disease.

PURPOSE OF REVIEW: Occupational and environmental exposures to metals can result in multiple pulmonary conditions. This article will review recent epidemiologic and mechanistic studies that have enhanced our understanding of the association between particular lung diseases and exposure to specific metals. RECENT FINDINGS: Recent studies have broadened our understanding of the mechanisms of lung diseases such as CBD in established industries and drawn attention to conditions that may arise from exposure to metals such as indium in developing technologies. New diagnostic techniques such as elemental tissue analysis may help establish a diagnosis of metal-induced occupational lung disease. Electronic cigarette devices, environmental pollutants, and the growing use of nanoparticle-sized metals pose additional risks to workers and consumers. SUMMARY: Recognizing the risks of pulmonary disease in workers exposed to metals and performing a thorough occupational history and diagnostic work-up in patients with unexplained respiratory findings is necessary to promote understanding and prevention of metal-induced lung disease.

Granulometry, microbial composition and biological activity of dusts collected in French dairy farms.

BACKGROUND: Dairy working increases the prevalence of lower airway respiratory diseases, especially COPD and asthma. Epidemiological studies have reported that chronic inhalation of organic dusts released during specific daily tasks could represent a major risk factor for development of these pathologies in dairy workers. Knowledge on size, nature and biological activity of such organic dusts remain however limited. OBJECTIVE: To compare size distribution, microbial composition and cellular effects of dusts liberated by the spreading of straw bedding in five French dairy farms located in Brittany. RESULTS: Mechanized distribution of straw bedding generated a cloud of inhalable dusts in the five dairy farms' barns. Thoracic particles having a 3-7.5µm size constituted 58.9-68.3% of these dusts. Analyses of thoracic dusts by next generation sequencing showed that the microbial dust composition differed between the five French farms, although Actinobacteria, Bacteroidetes, Firmicutes and Proteobacteria represent more than 97.5% of the bacterial phyla detected in each sample. Several bacteria genera comprising of human pathogenic species, such as Pseudomonas, Staphylococcus, Thermoactinomyces or Saccharopolyspora were identified. Cladosporium and Alternaria fungal genera, which are potent environmental determinants of respiratory symptoms, were detected in dusts collected in the five farms and their levels reached 15.5-51.1% and 9-24.7% of assignable fungal sequences in each sample, respectively. Finally, all dust samples significantly and strongly increased the expression of the pro-inflammatory TNF-α, IL-1ß, IL-6 and IL-8 cytokines at both mRNA and protein levels in human monocyte-derived macrophages. Their effects were dose-dependent and detectable from 1µg/ml. The intensity of the macrophage responses however differed according to the samples. CONCLUSIONS: Our results strengthen the hypothesis that organic dusts released during the distribution of straw bedding are mainly constituted of thoracic particles which are small enough to deposit on lower bronchial epithelium of dairy farmers and induce inflammation.

Progress with Structure-Activity Relationship modelling of occupational chemical respiratory sensitizers.

PURPOSE OF REVIEW: This appraises currently available computer-based ('in silico') models relating the molecular structure of low molecular weight compounds to their respiratory sensitization hazard. The present review places focus on the two main applications of such structure--activity relationship (SAR) models: hypotheses on disease mechanisms and toxicological prediction. RECENT FINDINGS: Analyses of the chemical structures of low molecular weight organic compounds known to have caused occupational asthma has led to the development of mechanistic alerts usually based on electrophilic reaction chemistry and protein cross-linking potential. Protein cross-linking potential has also been found to be a consistent feature of chemicals that have caused human cases of hypersensitivity pneumonitis. Stepwise iteration of quantitative SAR (QSAR) modelling has shown appreciable improvements in predictivity for occupational asthma hazard and useful prospects for practical application. A good case has also been made for the potential use of structural alert-based mechanistic SARs in predictive toxicology. SUMMARY: Further understanding of the molecular interactions between chemical respiratory sensitizers and components of human proteins have been obtained from in-vitro and in-silico techniques. There have been developments in both qualitative (mechanistic) SARs and QSARs, which offer potential for use in a predictive algorithm for the toxicological screening of industrial chemicals for respiratory sensitization potential.

Maternal Exposure to Occupational Asthmagens During Pregnancy and Autism Spectrum Disorder in the Study to Explore Early Development.

Maternal immune activity has been linked to children with autism spectrum disorder (ASD). We examined maternal occupational exposure to asthma-causing agents during pregnancy in relation to ASD risk. Our sample included 463 ASD cases and 710 general population controls from the Study to Explore Early Development whose mothers reported at least one job during pregnancy. Asthmagen exposure was estimated from a published job-exposure matrix. The adjusted odds ratio for ASD comparing asthmagen-exposed to unexposed was 1.39 (95 % CI 0.96-2.02). Maternal workplace asthmagen exposure was not associated with ASD risk in this study, but this result does not exclude some involvement of maternal exposure to asthma-causing agents in ASD.

Proteases in agricultural dust induce lung inflammation through PAR-1 and PAR-2 activation.

Workers exposed to aerosolized dust present in concentrated animal feeding operations (CAFOs) are susceptible to inflammatory lung diseases, such as chronic obstructive pulmonary disease. Extracts of dust collected from hog CAFOs [hog dust extract (HDE)] are potent stimulators of lung inflammatory responses in several model systems. The observation that HDE contains active proteases prompted the present study, which evaluated the role of CAFO dust proteases in lung inflammatory processes and tested whether protease-activated receptors (PARs) are involved in the signaling pathway for these events. We hypothesized that the damaging proinflammatory effect of HDE is due, in part, to the proteolytic activation of PARs, and inhibiting the proteases in HDE or disrupting PAR activation would attenuate HDE-mediated inflammatory indexes in bronchial epithelial cells (BECs), in mouse lung slices in vitro, and in a murine in vivo exposure model. Human BECs and mouse lung slice cultures stimulated with 5% HDE released significantly more of each of the cytokines measured (IL-6, IL-8, TNF-α, keratinocyte-derived chemokine/CXC chemokine ligand 1, and macrophage inflammatory protein-2/CXC chemokine ligand 2) than controls, and these effects were markedly diminished by protease inhibition. Inhibition of PARs also blunted the HDE-induced cytokine release from BECs. In addition, protease depletion inhibited HDE-induced BEC intracellular PKCα and PKCε activation. C57BL/6J mice administered 12.5% HDE intranasally, either once or daily for 3 wk, exhibited increased total cellular and neutrophil influx, bronchial alveolar fluid inflammatory cytokines, lung histopathology, and inflammatory scores compared with mice receiving protease-depleted HDE. These data suggest that proteases in dust from CAFOs are important mediators of lung inflammation, and these proteases and their receptors may provide novel targets for therapeutic intervention in CAFO dust-induced airways disease.

Man-made mineral fibers and interstitial lung diseases.

PURPOSE OF REVIEW: Manufactured (artificial) fibers represent an important and continuously growing volume among substitutes to natural fibers. A major proportion of the population in an industrialized society has been, is, or will be in contact with these fibers. The fibrous configuration of asbestos is well recognized as being an important parameter in toxicity, and now that of synthetic fibers is also suspected of inducing serious health effects on the respiratory system. There is an ongoing debate about the actual fibrogenic effect of these man-made mineral fibers (MMMFs) in humans. RECENT FINDINGS: Several case reports have demonstrated the biopersistance of MMMFs in the lung of workers who were exposed to rock wool or fiberglass for long periods of time and were diagnosed with interstitial pulmonary fibrosis. A 20-year follow up also identified refractory ceramic fibers in workers' lung tissue, with significant association between cumulative fiber exposure and radiographic pleural changes. Newly emerging man-made fiber industries appear to induce new types of occupational diseases. SUMMARY: Exposure of workers in MMMFs production plants is correlated to high risk for developing pneumoconiosis. Large epidemiological studies are needed in order to determine dose metrics for risk assessment and management.

A stone miner with both silicosis and constrictive pericarditis: case report and review of the literature.

BACKGROUND: The working environment of stone miners has been believed to cause their susceptibility to respiratory diseases. Silicosis is an occupational disease caused by exposure to crystalline silica dust which is marked by inflammation and scarring in the lung. The immune system boosted after the silica invasion led to self-damage and lay the foundation of silicosis pathogenesis. Silicosis coexisting with other diseases in one patient has been reported, however, was not reported to coexist with constrictive pericarditis. We, for the first time, reported a patient with silicosis and constrictive pericarditis and thought the immune response was probably the link between the two. CASE PRESENTATION: A 59-year-old Chinese stone miner complained of chest distress was found to have lung nodules which were found to be silica deposits by biopsy. This patient was also found to have constrictive pericarditis at the same time. Later surgical decortication cured his symptoms. CONCLUSION: We provided the first case having constrictive pericarditis concomitant with silicosis. A probable link between the two diseases was the immune response boosted by the silica deposits.

Sensitisation to cereal flour allergens is a major determinant of elevated exhaled nitric oxide in bakers.

OBJECTIVE: Various studies of the usefulness of fractional exhaled nitric oxide (FeNO) in occupational settings remain inconclusive. The objective was to investigate the determinants of increased FeNO in bakery workers. METHODS: A cross-sectional study of 424 supermarket bakery workers used a questionnaire and serum specific IgE to wheat, rye and α-amylase. FeNO during the work shift were assessed using a hand-held portable sampling device (NIOX MINO). RESULTS: The median FeNO was 15 ppb, in atopics 21 ppb and current smokers 12 ppb. Increased FeNO was strongly associated with IgE to wheat independent of smoking and atopy status. In the multivariate model, IgE to wheat, current smoking, atopy and age were significantly associated with FeNO. Stratified analysis in a subgroup of atopic non-smokers demonstrated the strongest relationship between FeNO and various clinical endpoint such as wheat (OR=9.43) or rye (OR=11.76) sensitisation, work-related allergic rhinitis (OR=8.13) or asthma (OR=5.44), and probable baker's asthma (OR=6.72). CONCLUSIONS: Sensitisation to cereal flour allergens rather than asthma symptoms is a major determinant of elevated FeNO among bakers. This relationship is modified by atopy and current smoking status.

Occupational exposure to airborne fungi in two Croatian sawmills and atopy in exposed workers.

Airborne fungi were collected over a one year period at 2-month intervals at 2 sawmills in Croatia (SM 1 and SM 2) processing mainly beech wood and oak wood. A questionnaire concerning respiratory symptoms and skin prick test (SPT) with common inhalatory allergens and moulds Cladosporium herbarum, Alternaria alternata, Aspergillus niger, Penicillium notatum, and Rhizopus nigricans were performed in 96 workers from the same sawmills. Average concentrations of airborne fungi were 1,696-7,316 cfu/m(3) in SM 1 and 1,706-4,819 cfu/m(3) in SM 2, respectively. Health hazardous levels of airborne fungi (above 10 4 /m(3)) were present only in SM 1. These levels were related to saw working sites and were season-dependent, i.e. present only during the summer. Penicillium (50-100%), Paecilomyces (43-100%) and Chrysonilia (33-100%) dominated among 17 fungal genera identified in both sawmills. Symptoms of rhinitis, asthma, and dry cough were most frequently recorded among analysed workers. SPT to moulds was negative in all tested workers, except one positive to R. nigricans, indicating that moderate airborne fungi levels found in the analysed sawmills were not related to IgE-mediated sensitization to moulds in exposed workers, even in atopics. Atopy was present among woodworkers in similar proportions to the general population of Croatia, suggesting that the wood-processing industry is not selective for atopic workers.

Systematic review: Progression of beryllium sensitization to chronic beryllium disease.

BACKGROUND: The relevance of beryllium sensitization testing for occupational health practice and prevention is unclear. AIMS: To analyse the natural course of beryllium sensitization and clarify the prognosis following cessation of exposure among sensitized workers. METHODS: An electronic literature search was conducted in PubMed, Embase, Toxline and Cochrane databases supplemented by a manual search. Data abstraction and study quality assessment with adapted guideline checklists were performed independently by three reviewers. Seven studies met the eligibility criteria and were included in the systematic review; however, six of the seven studies were of low methodological quality. RESULTS: A substantial (although not specifically quantifiable) proportion of beryllium-sensitized employees will develop chronic beryllium disease (CBD). To date, it is unknown if cessation of exposure in sensitized workers reduces the progression rate to CBD. CONCLUSIONS: To determine the utility of regular assessments for beryllium sensitization among exposed workers, there is a need for prospective studies. This should include detailed and continuous exposure monitoring, regular tests for beryllium sensitization and a thorough diagnostic evaluation of sensitized workers to confirm or exclude CBD.

Symptoms, spirometry, and serum antibody concentrations among compost workers exposed to organic dust.

Work-related symptoms and diseases of 190 currently exposed compost workers, 59 former compost workers, and 38 nonexposed control subjects were investigated in a cross-sectional study. Using a standardized questionnaire, participants were asked for work-related symptoms, exposures to bioaerosols, atopic diseases, and smoking habits. The subjects underwent a physical examination and a lung function test. In addition, total immunoglobulin (Ig) E, IgE specific to environmental allergens and moulds, and IgG specific to molds and actinomycetes were quantified. Compared to controls, compost workers suffered more often from cough and irritation of the eyes in terms of mucosal membrane irritation (MMI). Former compost workers reported similar work-related complaints, but most MMI symptoms had improved after termination of bioaerosol exposure. In contrast, cough and dyspnea persisted, indicating a chronic process. Lung function parameters of compost workers were within the reference ranges. Nevertheless, forced vital capacity (FVC) was significantly lower than for controls. Specific IgE to environmental allergens and molds was positive in 25.3% and 7.4%, respectively, of currently exposed compost workers. There were no marked differences in IgE and IgG concentrations among the three groups. Compost workers suffered with a higher frequency from cough and MMI symptoms. The findings that MMI symptoms improved in former compost workers after leaving the job confirmed the association with bioaerosol exposure. Further, the reduced FVC may be produced by this exposure. There was no higher frequency of mold sensitization in the group of compost workers compared to controls, which may be an indication of a healthy worker survivor effect.

IgG to various beta-glucans in a human adult population.

BACKGROUND: Fungal ß-(1,3)-glucans are pro-inflammatory agents, and exposures to ß-(1,3)-glucans are associated with respiratory tract symptoms. IgG anti-(1,3)-glucan titers are measured in diagnosis of fungal infections. Although other ß-glucan structures exist, like ß-(1,6)-glucans, little is known about their antigenic or pro-inflammatory properties. We aimed to investigate IgG titers and specificities in human sera against different ß-glucans with varying structures. METHODS: IgG anti-ß-glucan was measured by enzyme immunoassay in a random sample of 40 sera from healthy adults, with a panel of 8 differently structured glucans. In a subsequent larger series, IgG anti-ß-(1,6)-glucan was measured in a random sample of 667 sera from three occupational populations with different organic dust exposures. Possible determinants of IgG anti-ß-(1,6)-glucan titers were explored with linear-regression analysis. RESULTS: We found wide variation in anti-ß-glucan IgG levels. The highest titers were found for pure ß-(1,6)-glucan pustulan. Moderate to strong reactions with other ß-(1,6)-containing structures appeared to be due to cross-reacting anti-ß-(1,6)-glucan antibodies. Surprisingly, the mean IgG anti-ß-(1,6)-glucan titer was significantly lower in agricultural workers - with highest organic dust exposure - than in spray painters and bakery workers. Smoking status was associated with lower IgG anti-ß-(1,6)-glucan titers in all populations. CONCLUSIONS: IgG to ß-(1,3)- and ß-(1,6)-glucans can be found in normal human sera. ß-(1,6)-glucans appear to be much more potent antigens. The health impact of high anti-ß-(1,6)-glucan antibody levels remains unclear and further investigations are needed.

Influence of the environment and occupational exposure on the occurrence of Q fever.

Q fever, which is caused by Coxiella bumetii, is a worldwide zoonotic infectious disease and ruminants are the main reservoir for human infections. Humans become infected primarily by inhaling aerosols that are contaminated with C. bumetii. Ingestion (particularly drinking raw milk) and person-to-person transmission are minor routes. Animals shed the bacterium in urine and faeces, and in very high concentrations in birth by-products. The bacterium persists in the environment in a resistant spore-like form which may become airborne and transported long distances by the wind. Q fever is considered primarily an occupational disease of workers in close contact with farm animals or processing their products, however, it may occur also in persons without direct contact. To prevent the introduction and spread of Q fever infection, preventive measures should be implemented including immunisation with currently available vaccines of domestic animals and humans at risk.

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.

Exposure to formaldehyde and its potential human health hazards.

A widely used chemical, formaldehyde is normally present in both indoor and outdoor air. The rapid growth of formaldehyde-related industries in the past two decades reflects the result of its increased use in building materials and other commercial sectors. Consequently, formaldehyde is encountered almost every day from large segments of society due to its various sources. Many governments and agencies around the world have thus issued a series of standards to regulate its exposure in homes, office buildings, workshops, public places, and food. In light of the deleterious properties of formaldehyde, this article provides an overview of its market, regulation standards, and human health effects.

Solubility and chemistry of materials encountered by beryllium mine and ore extraction workers: relation to risk.

OBJECTIVE: Beryllium mine and ore extraction mill workers have low rates of beryllium sensitization and chronic beryllium disease relative to the level of beryllium exposure. The objective was to relate these rates to the solubility and composition of the mine and mill materials. METHOD: Medical surveillance and exposure data were summarized. Dissolution of BeO, ore materials and beryllium hydroxide, Be(OH)(2) was measured in synthetic lung fluid. RESULT: The ore materials were more soluble than BeO at pH 7.2 and similar at pH 4.5. Be(OH)(2) was more soluble than BeO at both pH. Aluminum dissolved along with beryllium from ore materials. CONCLUSION: Higher solubility of beryllium ore materials and Be(OH)(2) at pH 7.2 might shorten particle longevity in the lung. The aluminum content of the ore materials might inhibit the cellular immune response to beryllium.

[Evaluation of occupational allergic diseases of the respiratory tract].

The paper presents the basic etiological and pathogenetic aspects of occupational allergic diseases of the respiratory tract, discusses the clinical course, diagnosis, and priorities of the prevention of allergic diseases of the upper airways and bronchopulmonary apparatus from the action of industrial allergens.

Occupational mouse allergen exposure among non-mouse handlers.

This study assessed mouse allergen exposure across a range of jobs, including non-mouse handling jobs, at a mouse facility. Baseline data from 220 new employees enrolled in the Jackson Laboratory (JAXCohort) were analyzed. The baseline assessment included a questionnaire, allergy skin testing, and spirometry. Exposure assessments consisted of collection of two full-shift breathing zone air samples during a 1-week period. Air samples were analyzed for mouse allergen content, and the mean concentration of the two shifts represented mouse allergen exposure for that employee. The mean age of the 220 participants was 33 years. Ten percent reported current asthma and 56% were atopic. Thirty-eight percent were animal caretakers, 20% scientists, 20% administrative/support personnel, 10% materials/supplies handlers, and 9% laboratory technicians. Sixty percent of the population handled mice. Eighty-two percent of study participants had detectable breathing zone mouse allergen, and breathing zone mouse allergen concentrations were 1.02 ng/m³ (0.13-6.91) (median [interquartile range (IQR)]. Although mouse handlers had significantly higher concentrations of breathing zone mouse allergen than non-handlers (median [IQR]: 4.13 ng/m³ [0.69-12.12] and 0.21 ng/m³ [below detection (BD)-0.63], respectively; p < 0.001), 66% of non-handlers had detectable breathing zone mouse allergen. Mouse allergen concentrations among administrative/support personnel and materials/supplies handlers, jobs that generally do not entail handling mice, were median [IQR]: 0.23 ng/m³ [BD-0.59] and 0.63 ng/m³ [BD-18.91], respectively. Seventy-one percent of administrative/support personnel, and 68% of materials/supplies handlers had detectable breathing zone mouse allergen. As many as half of non-mouse handlers may have levels of exposure that are similar to levels observed among mouse handlers.