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.

Evaluation of chemical-specific IgG antibodies in male workers from a urethane foam factory.

BACKGROUND: Plastic resins are complex chemicals that contain toluene diisocyanate (TDI) and/or trimellitic anhydride (TMA), which cause occupational allergies (OA), including respiratory allergies. Serum IgGs against TDI and TMA have been suggested as potential markers of the exposure status and as exploring cause of OA. Although TDI-specific IgG has been examined for suspected OA, TMA-specific IgG is not commonly evaluated in a urethane foam factory. This study therefore investigated both TDI- and TMA-specific IgGs in suspected OA patients and to evaluate the usefulness of the measurement of multiple chemical-specific IgG measurement for practical monitoring. METHODS: Blood samples were collected from two male workers who developed respiratory allergies supposedly caused by occupational exposure to TDI and/or TMA for the presence of TDI- and TMA-specific IgGs. In addition, blood samples from 75 male workers from a urethane foam factory, along with 87 male control subjects, were collected in 2014 and tested for the same IgGs in 2014. The presence and levels of TDI- and TMA-specific serum IgGs were measured using dot blot assays. RESULTS: We found that controls had mean concentrations of TDI- and TMA-specific IgGs of 0.98 and 2.10 µg/mL, respectively. In the two workers with respiratory allergies, the TDI-specific IgG concentrations were 15.6 and 9.51 µg/mL, and TMA-specific IgG concentrations were 4.56 and 14.4 µg/mL, which are clearly higher than those in controls. Mean concentrations of TDI- and TMA-specific IgGs in the factory workers were 1.89 and 2.41 µg/mL, respectively, and are significantly higher than those of the controls (P < 0.001 and P < 0.026 for TDI- and TMA-specific IgGs, respectively). CONCLUSION: The workers suspected of OA showed an evidently high level of TDI- and TMA-specific IgG, and these levels in workers at the urethane foam factory were also significantly higher than those in controls. In conclusion, the measurement of TDI- and TMA-specific IgG among workers using plastic resins is helpful to monitor their exposure status.

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.

Association of Endotoxin and Allergens with Respiratory and Skin Symptoms: A Descriptive Study in Laboratory Animal Workers.

BACKGROUND: In laboratory animal work, allergens are classically considered to play a prominent role in generation of respiratory and skin symptoms. However, recent development may have changed working conditions and require an updating of preventive measures. OBJECTIVE: In workers exposed to a range of animals besides laboratory mice and rats the relative role of endotoxin, irritants, and allergens in symptom generation was assessed for updating preventative measures and health surveillance. METHODS: Eligible workers were recruited from university units in which exposure to rats and/or mice, occurrence of respiratory and/or skin symptoms, and/or a history of animal bites had been reported. Exposure to endotoxin and rat and mouse allergen was assessed (71 half-day personal samples). 'Symptomatic' was defined by work-related ocular, nasal, respiratory, or skin symptoms. A concentration of specific IgE against rat or mouse (e87 and e88) ≥0.35 kU/l defined sensitization. Sensitivity analyses examined the effect of alternative exposure indicators and definitions of 'sensitized' and 'symptomatic'. RESULTS: From 302 eligible workers, 177 participated. There were 121 and 41 workers in the asymptomatic and non-sensitized and symptomatic but non-sensitized group, respectively. Eight subjects were symptomatic and sensitized. Six sensitized subjects were asymptomatic. One participant could not be assigned to a subgroup. Airborne endotoxin and allergen concentrations were mostly below 20 EU m-3 or the detection limit, respectively. Clinical history showed that irritants and sensitizers other than mouse/rat allergen or endotoxin were a major cause of symptoms. Results were sensitive to the selected exposure indicator and the definition of 'symptomatic'. CONCLUSIONS: Health surveillance programs need to be adapted to include a larger range of allergens and pay more attention to irritants.

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.

Cross-Sectional Study on Nonmalignant Respiratory Morbidity due to Exposure to Synthetic Amorphous Silica.

OBJECTIVES: The aim of this study was to assess the health impact of chronic exposure to synthetic amorphous silica (SAS) on nonmalignant respiratory morbidity. METHODS: We used multiple linear and logistic regression models and Monte Carlo multimodel analyses of two exposure scenarios to evaluate the effect of cumulative exposure to inhalable SAS dust on symptoms, spirometry, and chest films in 462 male workers from five German SAS-producing plants. RESULTS: Exposure to SAS was associated with a reduction in forced vital capacity (FVC) in one of the two exposure scenarios but had no effect on forced expiratory volume in 1 second (FEV1) or FEV1/FVC in either exposure scenario. Monte Carlo analysis indicated a decline in FVC of -11 mL per 10 mg/m-years exposure (-6 to -0.4). Chest films showed no evidence of pneumoconiosis. CONCLUSION: This study provides limited evidence of minor dose-related effects of chronic exposure to SAS on lung function.

Toluene diisocyanate and methylene diphenyl diisocyanate: asthmatic response and cross-reactivity in a mouse model.

Both 2,4-toluene diisocyanate (TDI) and 4,4-methylene diphenyl diisocyanate (MDI) can cause occupational asthma. In this study, we optimized our mouse model of chemical-induced asthma in the C57Bl/6 mice strain using the model agent TDI. Furthermore, we validated MDI in this mouse model and investigated whether cross-reactivity between TDI and MDI is present. On days 1 and 8, C57Bl/6 mice were dermally treated (20 µl/ear) with 3 % MDI, 2 % TDI or the vehicle acetone olive oil (AOO) (3:2). On day 15, they received a single oropharyngeal challenge with 0.04 % MDI, 0.01 % TDI or the vehicle AOO (4:1). One day later, airway hyperreactivity (AHR) and pulmonary inflammation in the bronchoalveolar lavage (BAL) were assessed. Furthermore, total serum IgE levels, lymphocyte subpopulations in auricular lymph nodes and cytokine levels in supernatants of lymphocytes were measured. Both dermal sensitization with TDI or MDI resulted in increased total serum IgE levels along with T and B cell proliferation in the auricular lymph nodes. The auricular lymphocytes showed an increased release of both Th2 and Th1 cytokines. Mice sensitized and challenged with either TDI or MDI showed AHR, along with a predominant neutrophil lung inflammation. Mice sensitized with MDI and challenged with TDI or the other way around showed no AHR, nor BAL inflammation. Both TDI and MDI are able to induce an asthma-like response in this mouse model. However, cross-reactivity between both diisocyanates remained absent.

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.

Influence of 5 different caging types and the use of cage-changing stations on mouse allergen exposure.

Animal allergens constitute a serious health risk in laboratory animal facilities. To assess possibilities for allergen reduction by technical and organizational measures, we studied personnel exposure to mouse urinary aeroallergens in an animal facility with a holding capacity of 30,000 cages. Short-term (2 h) and intermediate-term (12 h) stationary samples (n = 107) and short-term (2 h) personnel samples (n = 119) were collected on polytetrafluorethylene filters by using air pumps. Long-term (14 d) stationary dust samples containing airborne allergens (n = 165) were collected with electrostatic dust fall collectors (EDC). Mouse allergens were quantified by ELISA. Personnel samples were collected during bedding disposal and refilling of clean cages as well as during cage changing with and without use of cage-changing station. Animal rooms were equipped with either open cages, cages with a soft filter top, cages with a rigid filter top (static microisolation caging), or with individually ventilated cages (IVC) with either a sealed or nonsealed lid, each in positive- or negative-pressure mode. Highest personnel allergen exposure was detected during cage change and emptying of soiled cages. Allergen concentrations were lowest in rooms with sealed IVC under positive or negative pressure, with unsealed IVC under negative pressure, and with static microisolation caging. The use of cage-changing stations and a vacuum bedding-disposal system reduced median personnel exposures 14- to 25-fold, respectively. Using sealed IVC and changing stations minimized allergen exposure, indicating that state-of-the-art equipment reduces exposure to mouse allergens and decreases health risks among animal facility personnel.

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.

The hapten-atopy hypothesis III: the potential role of airborne chemicals.

One explanation for the large increase in the prevalence of atopic disease in developed countries during the last 50 years is the 'hygiene hypothesis'. This proposes that a reduced exposure to pathogenic microorganisms at a key period(s) during development results in the maintenance or acquisition of an atopic phenotype. Alternatively, or additionally, we have postulated that increased exposure to chemicals generally, and to irritant/haptenic chemicals in particular, during critical windows of maternal pregnancy/early life have also contributed to changes in the prevalence of atopic disease. Having previously reviewed the potential roles of oral and cutaneous exposure to chemicals on the subsequent diagnosis of atopic disease, we here consider possible evidence of a role for exposure to airborne chemicals as a contributory factor in acquired susceptibility to atopic allergy. After controlling for known confounders, five specific maternal occupations during pregnancy have been implicated as being associated with subsequent atopic disease in the offspring. Each of these occupations is characterized by high and persistent exposure to airborne chemicals. High-level exposure to volatile organic compounds in the domestic environment, either during pregnancy or in early life, is also associated with development of childhood atopic disease. Similarly, sustained exposure to airborne chlorinated chemicals from swimming pools during childhood has been associated with the development of atopic allergy. A possible immunological basis for these associations is that exposure to certain airborne chemicals, even at low levels, can result in the delivery of 'danger' signals that, in turn, bias the immune response towards the selective induction or maintenance of preferential T helper 2-type immune responses consistent with the acquisition of allergic sensitization.

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.

Evaluation of the sensitisation to grains and its pulmonary impact in employees of the port of Brest silos.

BACKGROUND: Evaluation of the sensitisation and levels of exposure to grains and its pulmonary impact ina population of Brest port silo employees. MATERIALS AND METHODS: We included exposed workers. The study consisted of clinical examination witha standardised questionnaire, blood samples, prick-tests, and spirometry tests. The atmospheric concentrationof total dust in the workplace was also associated. RESULTS: Eight workers were included in the study. No case of occupational asthma was found, but 3 casesof occupational rhinitis were noted and occupational prick-tests were positive in 4 cases. The mean totaldust concentration in the three atmospheric samples was 4.87 mg/m3 for 8 hours but it was under thedetection limits for alveolar fractions. CONCLUSIONS: Port silo workers are exposed to total dust concentrations below the French legal limit (10 mg/m3) but higher than Canadian and American recommendations. Levels of exposure in our studyare similar to other studies developed in port silos. Symptoms developed by workers may be due to highexposure to dust with an irritant effect rather than an allergic effect. Despite this fact, a specific medicalsurvey is needed, and ventilation and respiratory masks have to be promoted for prevention.

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.

Immune functions of the garment workers.

BACKGROUND: Occupational exposure to cotton dust, fibers, metal fumes and different chemicals used in the aparrel manufacturing industries cause a wide range of physical and psychological health problems in the garment workers that may also affect their immune function. OBJECTIVE: To assess the immune system function in garment workers. METHODS: A total of 45 workers of a garment factory, and 41 control subjects, not exposed to the garment working environment were enrolled in this study. In the study subjects, the complement system function was assessed as bactericidal activity on Escherichia coli DH5α cells using the standard plate count method. Serum complement components C3 and C4 were measured by immunoprecipitation, and IgG was measured by immunonephelometry. RESULTS: The bactericidal activity of serum complement in the garment workers (range: 93.5%-99.9%) was significantly (p<0.01) lower than that in the controls (range: 98.6%-100%). The heat-inactivated serum of the workers showed a significantly enhanced bactericidal activity. In the garment workers, the mean levels of complement C3, and C4 were 1.75 and 0.26 g/L, respectively that were close to those of the controls. The mean IgG level in the garment workers was 13.5 g/L that was significantly (p<0.001) higher than that in the controls. CONCLUSION: Working in a garment factory may affect the immune system.