Alexandra M. Preisser

Circulating Mitochondrial DNA as Biomarker Linking Environmental Chemical Exposure to Early Preclinical Lesions Elevation of mtDNA in Human Serum after Exposure to Carcinogenic Halo-Alkane-Based Pesticides

There is a need for a panel of suitable biomarkers for detection of environmental chemical exposure leading to the initiation or progression of degenerative diseases or potentially, to cancer. As the peripheral blood may contain increased levels of circulating cell-free DNA in diseased individuals, we aimed to evaluate this DNA as effect biomarker recognizing vulnerability after exposure to environmental chemicals. We recruited 164 individuals presumably exposed to halo-alkane-based pesticides. Exposure evaluation was based on human biomonitoring analysis; as biomarker of exposure parent halo-methanes, -ethanes and their metabolites, as well as the hemoglobin-adducts methyl valine and hydroxyl ethyl valine in blood were used, complemented by expert evaluation of exposure and clinical intoxication symptoms as well as a questionnaire. Assessment showed exposures to halo alkanes in the concentration range being higher than non-cancer reference doses (RfD) but (mostly) lower than the occupational exposure limits. We quantified circulating DNA in serum from 86 individuals with confirmed exposure to off-gassing halo-alkane pesticides (in storage facilities or in home environment) and 30 non-exposed controls, and found that exposure was significantly associated with elevated serum levels of circulating mitochondrial DNA (in size of 79 bp, mtDNA-79, p = 0.0001). The decreased integrity of mtDNA (mtDNA-230/mtDNA-79) in exposed individuals implicates apoptotic processes (p = 0.015). The relative amounts of mtDNA-79 in serum were positively associated with the lag-time after intoxication to these chemicals (r = 0.99, p<0.0001). Several months of post-exposure the specificity of this biomarker increased from 30% to 97% in patients with intoxication symptoms. Our findings indicate that mitochondrial DNA has a potential to serve as a biomarker recognizing vulnerable risk groups after exposure to toxic/carcinogenic chemicals.

Occupational Screening for Tuberculosis and the Use of a Borderline Zone for Interpretation of the IGRA in German Healthcare Workers

Introduction Healthcare workers (HCWs) in low incidence countries with contact to patients with tuberculosis (TB) are considered a high-risk group for latent TB infection (LTBI) and therefore are routinely screened for LTBI. The German Occupational TB Network data is analyzed in order to estimate the prevalence and incidence of LTBI and to evaluate putative risk factors for a positive IGRA and the performance of IGRA in serial testing. Methods 3,823 HCWs were screened with the Quantiferon Gold in Tube (QFT) at least once; a second QFT was performed on 817 HCWs either in the course of contact tracing or serial examination. Risk factors for a positive QFT were assessed by a questionnaire. Results We observed a prevalence of LTBI of 8.3%. Putative risk factors for a positive QFT result were age >55 years (OR 6.89), foreign country of birth (OR 2.39), personal history of TB (OR 6.23) and workplace, e.g. internal medicine (OR 1.40), infection ward (OR 1.8) or geriatric care (OR 1.8). Of those repeatedly tested, 88.2% (721/817) tested consistently QFT-negative and 47 were consistently QFT-positive (5.8%). A conversion was observed in 2.8% (n = 21 of 742 with a negative first QFT) and a reversion occurred in 37.3% (n = 28 of 75 with a positive first QFT). Defining a conversion as an increase of the specific interferon concentration from <0.2 to >0.7 IU/ml, the conversion rate decreased to 1.2% (n = 8). Analogous to this, the reversion rate decreased to 18.8% (n = 9). Discussion In countries with a low incidence of TB and high hygiene standards, the LTBI infection risk for HCWs seems low. Introducing a borderline zone from 0.2 to ≤0.7 IU/ml may help to avoid unnecessary X-rays and preventive chemotherapy. No case of active TB was detected. Therefore, it might be reasonable to further restrict TB screening to HCWs who had unprotected contact with infectious patients or materials.

Tuberculosis in healthcare workers – a narrative review from a German perspective

IntroductionDespite the decline of tuberculosis in the population at large, healthcare workers (HCW) are still at risk of infection.MethodsIn a narrative review the TB risk in HCW and preventive measures are described, with the focus on epidemiology and Occupational Safety and Health (OSH) regulations in Germany.ResultsThere is an increased risk of infection not only in pneumology and laboratories with regular contact with tuberculosis patients or infectious materials. Epidemiological studies have also verified an increased risk of infection from activities that involve close contact with patients’ breath (e.g. bronchoscopy, intubation) or close contact with patients in need of care in geriatric medicine or geriatric nursing. In occupational disease claim proceedings on account of tuberculosis, the burden of proof can be eased for insured persons who work in these or other comparable fields. Forgoing evidence of an index person as a source of infection has led to a doubling of the rate of cases of tuberculosis recognised as an occupational disease and has halved the duration of occupational disease claim proceedings in Germany. For several years now, it has been possible to use the new interferon-y release assays (IGRAs) to diagnose a latent tuberculosis infection (LTBI) with significantly greater validity than with the traditional tuberculin skin test (TST). However, variability of the IGRAs around the cut-off poses problems especially in serial testing of HCWs. At around 10%, LTBI prevalence in German healthcare workers is lower than had been assumed. It can make sense to treat a recent LTBI in a young healthcare worker so as to prevent progression into active tuberculosis. If the LTBI is occupational in origin, the provider of statutory accident insurance can cover the costs of preventive treatment. However, little is known about disease progression in HCWs with positive IGRA sofar.ConclusionTB screening in HCWs will remain an important issue in the near future even in low incidence, high income countries, as active TB in HCWs is often due to workplace exposure. The IGRAs facilitate these screenings. However, variability of IGRA results in serial testing of HCWs need further investigations.

Surprises perilous: Toxic health hazards for employees unloading fumigated shipping containers

The fumigation of freight containers to protect transported goods from fungal and pest infestation has increased worldwide in the last five years due to international regulations requiring fumigation or heat treatment of wooden packaging material and dunnage. We have found in 2008 that every sixth container and its contents do retain harmful concentrations of various fumigants and chemicals, representing a significant health risk for port and transport workers, customs officials, warehousemen, store employees and consumers. The shipping documents of these containers did not provide any information about the fumigation procedure or the used fumigant. We report here the cases of 26 patients introduced to our outpatient clinic with presumed intoxication to fumigants, or with symptoms due to inhaling the air out of fumigated containers. All patients were examined from 2007 to 2010 according to a standardized comprehensive diagnostic program. We were able to confirm the diagnosis based on typical symptoms and extensive clinical examination; by laboratory analysis we identified ethylene dichloride, methyl bromide, phosphine and methylene chloride. The predominant symptoms were headaches, concentration and memory problems, dizziness and nausea, irritation of the skin and mucous membranes and a reduced ability to do exercise. In addition to the neurological and neuropsychological impairments our analyses verified the development of reactive airways dysfunction syndrome (RADS) in 14 of 26 patients with long lasting symptoms due to their contact with fumigants. Intoxications with fumigants are serious and could be avoided. These systematical explored cases show the sustainable impact for health and socio-economic wellbeing. These findings also emphasize the necessity for international standards on permitted fumigants, appropriate labeling in the shipping documents and handling of fumigated containers.

Psychische Belastung von Beschäftigten in der deutschen Offshore-Windindustrie

ZusammenfassungDer Artikel gibt eine Übersicht über den aktuellen Forschungsstand zur psychischen Belastung von Beschäftigten in der deutschen Offshore-Windindustrie. Trotz der besonderen Herausforderungen, die die Arbeit im Offshore-Bereich mit sich bringt, existieren zum gegenwärtigen Zeitpunkt kaum Erkenntnisse und keinerlei empirische Befunde zur psychischen Belastung von Beschäftigten in der deutschen Offshore-Windindustrie. Die bis dato verfügbare Literatur deutet jedoch darauf hin, dass Offshore-Beschäftigte bei ihrer Arbeit zahlreichen psychischen Belastungsfaktoren ausgesetzt sind. Forschungstätigkeiten zur Analyse der psychischen Belastung von Beschäftigten in der deutschen Offshore-Windindustrie sowie zur Entwicklung bedarfsgerechter Maßnahmen der Gesundheitsförderung sind demnach dringend erforderlich.AbstractThe article gives an overview of the current state of research regarding mental stress among employees working in the German offshore wind industry. Despite the particular demands inherent to the offshore work environment, very little is known about the mental stress among offshore workers in the German offshore wind industry. To date, no research studies concerning this topic have been reported; however, the available literature suggests that offshore workers are confronted with numerous psychological risk factors at work. Thus, further research is needed in order to investigate the mental stress among employees working in the German offshore wind industry and to develop applicable health promotion interventions.

IgE Reactivity, Work Related Allergic Symptoms, Asthma Severity, and Quality of Life in Bakers with Occupational Asthma

In Germany, bakers with occupational asthma willing to stay in their job are included in an interdisciplinary program of the Social Accident Insurance for Foodstuff and Catering Industry (BGN). The primary aim is to reduce flour dust exposure, and to provide adequate medical treatment. Our aim was to evaluate the programs effect on the diseases course using routinely collected data. Forty three bakers with allergic occupational asthma and with the available baseline level of IgE (f4, f5) were investigated. Changes in IgE related to wheat and rye flour exposure were measured by ImmunoCAP test during follow-up visits. A questionnaire on work-related allergic complaints (WRAC), the Asthma Control Test (ACT), a 10-point scale of asthma severity grade, and quality of life instruments (EQ-5D-5L, Mini-AQLQ) were administered. We found an improvement of asthma severity in 88.4 % of the bakers. WRAC were reported by 65 %; 77 % had good asthma control (ACT ≥ 20); and 81 % had regular asthma medication. A relevant reduction of ≥2 CAP-classes for both allergens was seen in 12 % of the subjects. Health-related and asthma-specific quality of life was high. We conclude that satisfactory asthma control is probably the result of adequate medical management. In a subgroup of bakers with decreased specific IgE, it may also be attributed to reduced allergen exposure.

Healthy offshore workforce? A qualitative study on offshore wind employees’ occupational strain, health, and coping

BackgroundOffshore work has been described as demanding and stressful. Despite this, evidence regarding the occupational strain, health, and coping behaviors of workers in the growing offshore wind industry in Germany is still limited. The purpose of our study was to explore offshore wind employees’ perceptions of occupational strain and health, and to investigate their strategies for dealing with the demands of offshore work.MethodsWe conducted 21 semi-structured telephone interviews with employees in the German offshore wind industry. The interviews were transcribed and analyzed in a deductive-inductive approach following Mayring’s qualitative content analysis.ResultsWorkers generally reported good mental and physical health. However, they also stated perceptions of stress at work, fatigue, difficulties detaching from work, and sleeping problems, all to varying extents. In addition, physical health impairment in relation to offshore work, e.g. musculoskeletal and gastrointestinal complaints, was documented. Employees described different strategies for coping with their job demands. The strategies comprised of both problem and emotion-focused approaches, and were classified as either work-related, health-related, or related to seeking social support.ConclusionsOur study is the first to investigate the occupational strain, health, and coping of workers in the expanding German offshore wind industry. The results offer new insights that can be utilized for future research in this field. In terms of practical implications, the findings suggest that measures should be carried out aimed at reducing occupational strain and health impairment among offshore wind workers. In addition, interventions should be initiated that foster offshore wind workers’ health and empower them to further expand on effective coping strategies at their workplace.

Is the analysis of histamine and/or interleukin-4 release after isocyanate challenge useful in the identification of patients with IgE-mediated isocyanate asthma?

Isocyanates are a well-known and frequent cause of occupational asthma. The implementation of specific inhalation challenges (SICs) is the gold standard in asthma diagnosis supporting occupational case history, lung function testing, specific skin prick tests and the detection of specific IgE. However, the diagnosis is not always definitive. An interesting new approach, analyses of individual genetic susceptibilities, requires discrimination between a positive SIC reaction arising from IgE-mediated immune responses and one from other pathophysiological mechanisms. Hence, additional refinement tools would be helpful in defining sub-classes of occupational asthma and diagnosis. We used total IgE levels, specific IgE and SIC results for sub-classification of 27 symptomatic isocyanate workers studied. Some mutations in glutathione S-transferases (GSTs) are suspected either to enhance or to decrease the individual risk in the development of isocyanate asthma. Our patient groups were assessed for the point mutations GSTP1*I105V and GSTP1*A114V as well as deletions (null mutations) of GSTM1 and GSTT1. There seems to be a higher risk in developing IgE-mediated reactions when GSTM1 is deleted, while GSTT1 deletions were found more frequently in the SIC positive group. Blood samples taken before SIC, 30-60 min and 24h after SIC, were analyzed for histamine and IL-4, classical markers for the IgE-mediated antigen-specific activation of basophils or mast cells. We suggest that the utility of histamine measurements might provide an additional useful marker reflecting isocyanate-induced cellular reactions (although the sampling times require optimization). The promising measurement of IL-4 is not feasible at present due to the lack of a reliable, validated assay.

Diffusion Limitations of the Lung – Comparison of Different Measurement Methods

Pulmonary fibrosis leads to a decrease of oxygen diffusion, in particular during exercise. Bronchial obstruction also could decrease the partial pressure of oxygen (P(a)O(2)). In this study we investigated the validity of blood gas content, especially P(a)O(2) and P(a)O(2) affected by hyperventilation (P(a)O(2corr)) and alveolo-arterial oxygen gradient (P(A-a)O(2)) in comparison with the CO diffusion capacity (DLCO) in different lung diseases. A total of 250 subjects were studied (52.3 ± 12.5 year; F/M 40/210), among which there were 162 subjects with different lung disorders and 88 healthy controls. Pearsons correlation coefficients (r) of DLCO with P(a)O(2), P(a)O(2corr), and PA-aO(2) were analyzed in each group. The results show that the diagnostic power of P(A-a)O(2) against P(a)O(2corr) was equivalent, especially during exercise (r = -0.89 and -0.92, respectively). DLCO showed only weak correlations with P(a)O(2corr) and P(A-a)O(2) (r = 0.17 and -0.19, respectively). In conclusion, DLCO shows a better match with blood gas content during exercise than at rest during which it is routinely tested. Thus, the exercise test is advisable. The P(A-a)O(2) takes into account the level of ventilation, which makes it correlate better with DLCO rather than with blood gas content. The most significant problems in clinical evaluation of blood gas parameters during exercise are the insufficiently defined limits of normal-to-pathological range.

A cross-sectional survey of physical strains among offshore wind farm workers in the German exclusive economic zone

Objectives To assess the physical strains of employees in the German offshore wind industry, according to job type and phase of the wind farm (under construction or operation). Design Web-based cross-sectional survey. Setting Offshore wind farm companies operating within the German exclusive economic zone. Participants Male workers with regular offshore commitments and at least 28 days spent offshore in the past year (n=268). Outcome measures Physical strains (eg, climbing, noise, working overhead, with twisted upper body or in confined spaces, vibration, heavy lifting, humidity, odours). Results The most frequently mentioned physical strain was ’climbing’ with 63.8% of the respondents reporting to be always or frequently confronted with climbing and ascending stairs during offshore work. Work as a technician was associated with a greater exposition to noise, vibrations, humidity, cold, heat, chemical substances, lifting/carrying heavy loads, transport of equipment, working in non-ergonomic positions and in cramped spaces, as well as climbing. Indeed, statistical analyses showed that, after adjusting for phase of the wind farm, age, nationality, offshore experience, work schedule and type of shift, compared with non-technicians, working as a technician was associated with more frequently lifting/carrying of heavy loads (OR 2.58, 95% CI 1.58 to 4.23), transport of equipment (OR 2.06 95% CI 1.27 to 3.33), working with a twisted upper body (OR 2.85 95% CI 1.74 to 4.69), working overhead (OR 2.77 95% CI 1.67 to 4.58) and climbing (OR 2.30 95% CI 1.40 to 3.77). Working in wind farms under construction was strongly associated with increased and decreased exposure to humidity (OR 2.32 95% CI 1.38 to 3.92) and poor air quality (OR 0.58 95% CI 0.35 to 0.95), respectively. Conclusions Workers on offshore wind farms constitute a heterogeneous group, including a wide variety of occupations. The degree of exposure to detrimental physical strains varies depending on the type of job. Technicians are more exposed to ergonomic challenges than other offshore workers.