Biomonitoring of lead in blood of children living in a former mining area in Lower Saxony, Germany.

Environmental exposure to lead substantially decreased over the past decades. However, soil of former mining areas still contains high lead levels. We therefore performed a biomonitoring study among children living in two former mining communities in Lower Saxony, Germany. In these communities, soil contains lead levels of 1000 to 30,000 mg/kg. Overall, 75 children (6-10 years of age) attending the two primary schools of the study area took part in the study. Parents completed a short questionnaire on sociodemographics, and children provided capillary whole blood samples. We analysed lead using inductively coupled plasma tandem mass spectrometer. We compared the results to current German (20 µg/l for boys, 15 µg/l for girls) and US (35 µg/l) reference values. Potential associations between questionnaire information and lead results were tested using lead as continuous outcome and using lead dichotomized at the reference values. Finally, we analysed spatial patterns of elevated biomonitoring results. Of all children, 48% exceeded the German reference values for lead (5% expected) and 8% the US reference value (2.5% expected). Children 6-8 years of age were more likely to exceed German reference values (63%) than 9-10 year old children were (32%; pFisher = 0.01). No other questionnaire information was statistically significantly associated with biomonitoring results. Additionally, we did not find any indication of spatial clustering. In conclusion, we observed elevated blood lead levels in primary school children living in a former mining area. In the next step, exposure pathways need to be identified to implement effective public health measures.

Parental occupational exposures prior to conception and offspring wheeze and eczema during first year of life.

PURPOSE: Parental exposures prior to conception might influence asthma and allergy risk in offspring. As occupational exposures are established risk factors for asthma and allergies, we investigated if parental occupational exposures prior to conception cause wheeze and eczema in offspring during the first year of life. METHODS: We analysed data of 436 families from an offspring cohort based on a follow-up study of German participants of the International Study of Asthma and Allergies in Childhood (ISAAC). Offspring cohort data was collected between 2009 and 2019. Occupational exposures were based on participants' work histories and measured by a Job-Exposure-Matrix. We used Bayesian logistic regression models for analysis. Inference and confounder selection were based on directed acyclic graphs. RESULTS: In mothers, for both allergic and irritative occupational exposures prior to conception suggestive effects on offspring eczema during the first year of life were found (allergens: odds ratio (OR) 1.22, 95% compatibility interval (CI) 0.92-1.57; irritants: OR 1.36, 95% CI 0.99-1.77), while no relation with wheeze was suggested. CONCLUSIONS: Our results suggest that reduction of asthma-related occupational exposures might not only reduce the burden of disease for occupationally induced or aggravated asthma and allergies in employees but also in their children.

Work-related stress and atopic dermatitis: Results from the study on occupational allergy risks.

Chronic stress at work is ubiquitous in modern societies. However, its influence on atopic dermatitis (AD) has hardly been investigated. This study aimed to elucidate the association between work-related stress and AD via a longitudinal study. The analysis comprised data from three phases (2002-2003, 2007-2009, 2017-2018) of the prospective Study on Occupational Allergy Risks (SOLAR), including 1,240 young adults aged 16 to 18 years at baseline (61% female) who were originally recruited for the International Study of Asthma and Allergies in Childhood Phase II in 1995-1996. AD was assessed at all three phases based on self-reports of a physician's diagnosis and symptoms. Work-related stress was measured at all three periods using the work discontent and work overload scales from the Trier Inventory for the Assessment of Chronic Stress with adaptions to school and university. Generalized estimating equations were used to analyze the association between stress and AD, treating work discontent and work overload first as continuous and then as categorical exposure variables. We observed 50 AD cases (4%) at SOLAR I, 48 (4%) at SOLAR II, and 42 (3%) at SOLAR III. A one-point increase in the work discontent score was associated with an odds ratio (OR) for AD of 1.05 (95% confidence interval [CI], 1.00-1.10). The respective increase in the work overload score led to an OR of 1.03 (95% CI, 0.99-1.06). In the categorical analysis, there was no clear indication of elevated odds of AD in the highest vs. lowest exposure group (4th vs. 1st quartile: OR, 1.53; 95% CI, 0.92-2.53 for work discontent; OR, 1.38, 95% CI, 0.83-2.27 for work overload). Altogether, we observed limited to no evidence for an association between work-related stress and AD. Our study's ability to detect stronger evidence may have been compromised by shortcomings such as nondifferential misclassification of the outcome or insufficient statistical precision due to small numbers of AD cases. Another explanation could be that AD predominantly becomes evident in childhood, not in adulthood.

Residential proximity to oil and gas production sites and hematologic malignancies: A case-control study.

BACKGROUND: We investigated the association between residential proximity to oil and gas production sites and hematologic malignancies, due to a cancer cluster in the German state of Lower Saxony. METHODS: A registry-based case-control study was conducted including 3978 cases of hematologic malignancies diagnosed within 2013-2016 and 15,912 frequency-matched controls randomly drawn by population registries. Residential proximity to 5333 oil and gas production sites at the time of diagnosis was calculated. Unconditional logistic regression models were used to estimate the association between living within 1 km of any exposure site and developing a hematologic malignancy. Models were adjusted for matching variables sex, age group, district, and year of diagnosis as well as for proximity to main streets and to agricultural land. RESULTS: We found no association between the development of hematologic malignancies and the proximity to all oil and gas production sites (odds ratio: 0.97; 95% confidence interval: 0.85, 1.11). Focusing on gas production sites increased the odds of developing hematologic cancer (odds ratio: 1.19; 95% confidence interval: 0.97, 1.45). In stratified analyses, associations were stronger in women and for acute myeloblastic leukemia. We also found an association in the district where the initial cluster occurred. CONCLUSIONS: Our results suggest that residential proximity to oil and gas production is not a risk factor for all hematologic malignancies in general. Sporadic and past exposures are the most likely scenarios for mechanisms involving oil and gas production, leading to increased risk for certain subtypes of cancer in certain populations.

Trajectories of asthma and allergy symptoms from childhood to adulthood.

BACKGROUND: Phenotypes of asthma and allergic diseases are mainly studied separately for children and adults. To explore the role of adolescence and young adulthood, we investigated symptom trajectories at the transition from childhood into adulthood. METHODS: Latent class analysis (LCA) was conducted in a population initially recruited for the German arm of Phase II of the International Study of Asthma and Allergies in Childhood and followed-up three times until their early 30s (N=2267). Indicators included in LCA were 12-month prevalences of symptoms of wheeze, rhinoconjunctivitis, and eczema. Latent classes were further characterised regarding important traits such as skin prick tests. Logistic regression models were used to investigate associations with environmental determinants such as smoking and occupational exposures. RESULTS: Six latent classes were identified: an asymptomatic one as well as three with single and two with co-occurring symptoms. All trajectories essentially established between baseline assessment at around 10 years and the first follow-up at around 17 years. Probabilities for symptoms increased from childhood to adolescence, especially for wheeze-related latent classes, while they remained constant in adulthood. Wheeze-related latent classes were also positively associated with exposures during adolescence (e.g. active smoking). CONCLUSION: Distinct trajectories of asthma and allergy symptoms establish from childhood through adolescence and stabilize during early adulthood. This pattern was most notable in wheeze-related latent classes which also showed the strongest positive associations with environmental exposures in adolescence/young adulthood. Therefore, not only childhood but also adolescence is relevant for disease development and offers considerable potential for prevention and health promotion.

From first to second wave: follow-up of the prospective COVID-19 cohort (KoCo19) in Munich (Germany).

BACKGROUND: In the 2nd year of the COVID-19 pandemic, knowledge about the dynamics of the infection in the general population is still limited. Such information is essential for health planners, as many of those infected show no or only mild symptoms and thus, escape the surveillance system. We therefore aimed to describe the course of the pandemic in the Munich general population living in private households from April 2020 to January 2021. METHODS: The KoCo19 baseline study took place from April to June 2020 including 5313 participants (age 14 years and above). From November 2020 to January 2021, we could again measure SARS-CoV-2 antibody status in 4433 of the baseline participants (response 83%). Participants were offered a self-sampling kit to take a capillary blood sample (dry blood spot; DBS). Blood was analysed using the Elecsys® Anti-SARS-CoV-2 assay (Roche). Questionnaire information on socio-demographics and potential risk factors assessed at baseline was available for all participants. In addition, follow-up information on health-risk taking behaviour and number of personal contacts outside the household (N = 2768) as well as leisure time activities (N = 1263) were collected in summer 2020. RESULTS: Weighted and adjusted (for specificity and sensitivity) SARS-CoV-2 sero-prevalence at follow-up was 3.6% (95% CI 2.9-4.3%) as compared to 1.8% (95% CI 1.3-3.4%) at baseline. 91% of those tested positive at baseline were also antibody-positive at follow-up. While sero-prevalence increased from early November 2020 to January 2021, no indication of geospatial clustering across the city of Munich was found, although cases clustered within households. Taking baseline result and time to follow-up into account, men and participants in the age group 20-34 years were at the highest risk of sero-positivity. In the sensitivity analyses, differences in health-risk taking behaviour, number of personal contacts and leisure time activities partly explained these differences. CONCLUSION: The number of citizens in Munich with SARS-CoV-2 antibodies was still below 5% during the 2nd wave of the pandemic. Antibodies remained present in the majority of SARS-CoV-2 sero-positive baseline participants. Besides age and sex, potentially confounded by differences in behaviour, no major risk factors could be identified. Non-pharmaceutical public health measures are thus still important.

Prevalence and Risk Factors of Infection in the Representative COVID-19 Cohort Munich.

Given the large number of mild or asymptomatic SARS-CoV-2 cases, only population-based studies can provide reliable estimates of the magnitude of the pandemic. We therefore aimed to assess the sero-prevalence of SARS-CoV-2 in the Munich general population after the first wave of the pandemic. For this purpose, we drew a representative sample of 2994 private households and invited household members 14 years and older to complete questionnaires and to provide blood samples. SARS-CoV-2 seropositivity was defined as Roche N pan-Ig ≥ 0.4218. We adjusted the prevalence for the sampling design, sensitivity, and specificity. We investigated risk factors for SARS-CoV-2 seropositivity and geospatial transmission patterns by generalized linear mixed models and permutation tests. Seropositivity for SARS-CoV-2-specific antibodies was 1.82% (95% confidence interval (CI) 1.28-2.37%) as compared to 0.46% PCR-positive cases officially registered in Munich. Loss of the sense of smell or taste was associated with seropositivity (odds ratio (OR) 47.4; 95% CI 7.2-307.0) and infections clustered within households. By this first population-based study on SARS-CoV-2 prevalence in a large German municipality not affected by a superspreading event, we could show that at least one in four cases in private households was reported and known to the health authorities. These results will help authorities to estimate the true burden of disease in the population and to take evidence-based decisions on public health measures.

Third Follow-Up of the Study on Occupational Allergy Risks (SOLAR III) in Germany: Design, Methods, and Initial Data Analysis.

Introduction: Asthma and allergies are complex diseases affected by genetic and environmental factors, such as occupational and psychosocial factors, as well as interactions between them. Although childhood is a critical phase in the development of asthma and allergies, few cohort studies on occupational outcomes followed up participants from childhood onwards. We present design, methods, and initial data analysis for the third follow-up of SOLAR (Study on Occupational Allergy Risks), a prospective and population-based German asthma and allergy cohort. Methods: The SOLAR cohort was initially recruited in 1995-1996 for Phase II of the German branch of the International Study of Asthma and Allergies in Childhood (ISAAC II) and followed up three times since, in 2002-2003, 2007-2009, and 2017-2018. During the third follow-up (SOLAR III), participants were between 29 and 34 years old. Since SOLAR focuses on occupational exposures, follow-ups were conducted at important points in time of the development of participants' career. To evaluate the potential of selection bias, responders and non-responders were compared based on variables from earlier study phases. In responders, frequency and pattern of missing values were examined and compared within the subsets of paper and online versions of the used questionnaires. Results: In total, 1,359 participants completed the questionnaire of the third follow-up (47.3% of eligible participants). Initially, the cohort started with 6,399 participants from the ISAAC II questionnaire study. A selection process led to a study population that is more female, higher educated, smokes less and has a higher proportion of certain asthma and allergy symptoms (also in their parents) than the initial cohort. Pattern and frequency of missing values were different for paper and online questionnaires. Discussion: The third follow-up of the SOLAR cohort offers the opportunity to analyze the course of asthma and allergies and their associations to environmental, occupational and psychosocial risk factors over more than 20 years from childhood to adulthood. Selection processes within the cohort might lead to bias that needs to be considered in future analyses.

Publisher Correction to: Protocol of a population-based prospective COVID-19 cohort study Munich, Germany (KoCo19).

An amendment to this paper has been published and can be accessed via the original article.

Protocol of a population-based prospective COVID-19 cohort study Munich, Germany (KoCo19).

BACKGROUND: Due to the SARS-CoV-2 pandemic, public health interventions have been introduced globally in order to prevent the spread of the virus and avoid the overload of health care systems, especially for the most severely affected patients. Scientific studies to date have focused primarily on describing the clinical course of patients, identifying treatment options and developing vaccines. In Germany, as in many other regions, current tests for SARS-CoV2 are not conducted on a representative basis and in a longitudinal design. Furthermore, knowledge about the immune status of the population is lacking. Nonetheless, these data are needed to understand the dynamics of the pandemic and hence to appropriately design and evaluate interventions. For this purpose, we recently started a prospective population-based cohort in Munich, Germany, with the aim to develop a better understanding of the state and dynamics of the pandemic. METHODS: In 100 out of 755 randomly selected constituencies, 3000 Munich households are identified via random route and offered enrollment into the study. All household members are asked to complete a baseline questionnaire and subjects ≥14 years of age are asked to provide a venous blood sample of ≤3 ml for the determination of SARS-CoV-2 IgG/IgA status. The residual plasma and the blood pellet are preserved for later genetic and molecular biological investigations. For twelve months, each household member is asked to keep a diary of daily symptoms, whereabouts and contacts via WebApp. If symptoms suggestive for COVID-19 are reported, family members, including children < 14 years, are offered a pharyngeal swab taken at the Division of Infectious Diseases and Tropical Medicine, LMU University Hospital Munich, for molecular testing for SARS-CoV-2. In case of severe symptoms, participants will be transferred to a Munich hospital. For one year, the study teams re-visits the households for blood sampling every six weeks. DISCUSSION: With the planned study we will establish a reliable epidemiological tool to improve the understanding of the spread of SARS-CoV-2 and to better assess the effectiveness of public health measures as well as their socio-economic effects. This will support policy makers in managing the epidemic based on scientific evidence.

Nickel allergy is associated with wheezing and asthma in a cohort of young German adults: results from the SOLAR study.

BACKGROUND: Nickel allergy is the most prevalent contact allergy. It belongs to a different hypersensitivity type to asthma and rhinoconjunctivitis. The aim of this analysis was to assess whether self-reported nickel allergy is associated with incident wheezing, asthma and rhinoconjunctivitis in young German adults, taking into account potential effect modification by sex. METHODS: In total, 2051 (70.6%) participants aged 19-24 years took part in the second phase of SOLAR (Study on Occupational Allergy Risks), a follow-up study of ISAAC II (the second phase of the International Study of Asthma and Allergies in Childhood) in Germany. Self-reported nickel allergy, as well as having pierced ears, and the three outcomes incident wheezing, asthma and rhinoconjunctivitis, were analysed stratified for sex. Logistic regression adjusted for potential confounders was performed. RESULTS: An association between self-reported nickel allergy and incident wheezing was observed for men and women, while only in males did pierced ears show a significant association with the outcome (adjusted OR 2.26, 95% CI 1.10-4.62). Also only in males, self-reported nickel allergy was associated with elevated odds for incident asthma (adjusted OR 4.34, 95% CI 1.22-15.41). Neither in men nor in women was a significant association observed for incident rhinoconjunctivitis. CONCLUSION: Our results suggest that self-reported nickel allergy is associated with incident wheezing. Whether this association is due to environmental or genetic predisposition, or due to an overlap of the mechanisms of type I and type IV hypersensitivity, needs to be elucidated.

Association Between Occupational Exposure to Disinfectants and Asthma in Young Adults Working in Cleaning or Health Services: Results From a Cross-Sectional Analysis in Germany.

OBJECTIVE: To analyze the association of occupational disinfectants use with asthma and wheezing in young professionals. METHODS: Three hundred sixty-five participants from the German Study on Occupational Allergy Risks II aged 20 to 24 years and working in cleaning or health services answered a questionnaire on respiratory health, occupational exposure to disinfectants, and potential confounders. By logistic regression, we calculated the association between duration of occupational disinfectants exposure and doctor-diagnosed asthma, current asthma, and current wheezing. RESULTS: Individuals exposed to disinfectants for more than 12 months had almost three times the odds of doctor-diagnosed asthma compared with those not exposed (odds ratio [OR]: 2.99, 95% confidence interval [CI]: 1.36-6.55). CONCLUSIONS: Our findings provide some further evidence for an association between occupational exposure to disinfectants and asthma, indicating that this association can be seen already after the first year of exposure.

Work-related stress and incident asthma and rhinitis: results from the SOLAR study.

OBJECTIVES: This study analyzes the association of work-related stress with incident asthma and rhinitis in young adults with a special focus on gender-specific differences. METHODS: Incident asthma, wheezing and rhinitis were measured in a cohort of 2051 young German adults (aged 16-18 years at baseline) recruited by the prospective population-based SOLAR study (Study of Occupational Allergy Risks). Work-related stress was measured by the Trier Inventory for the Assessment of Chronic Stress (TICS). Two TICS scales, work overload and work discontent, were analysed. Logistic regression was conducted to calculate odds ratios (OR) and 95% confidence intervals (CI). RESULTS: In females, the odds for incident asthma were found to be 17% higher for each increase of the work discontent score by one point (OR 1.17, 95% CI 1.04-1.31). In males, no association was statistically significant. Incident rhinitis showed no association with any exposure variable. CONCLUSION: This study shows a link between work-related stress and incident asthma which seems to be confined to women. This study adds evidence about the association of work-related stress and asthma in young adults and can contribute to prevention for that particular age group.