Publications by authors named "Stefan Karrasch"

60 Publications

Subclinical cardiac impairment relates to traditional pulmonary function test parameters and lung volume as derived from whole-body MRI in a population-based cohort study.

Sci Rep 2021 Aug 9;11(1):16173. Epub 2021 Aug 9.

Department of Diagnostic and Interventional Radiology, Medical Center, University of Freiburg, Hugstetter Straße 55, 79106, Freiburg, Germany.

To evaluate the relationship of cardiac function, including time-volume-curves, with lung volumes derived from pulmonary function tests (PFT) and MRI in subjects without cardiovascular diseases. 216 subjects underwent whole-body MRI and spirometry as part of the KORA-FF4 cohort study. Lung volumes derived semi-automatically using an in-house algorithm. Forced expiratory volume in one second (FEV1), forced vital capacity (FVC), and residual volume were measured. Cardiac parameters derived from Cine-SSFP-sequence using cvi42, while left ventricle (LV) time-volume-curves were evaluated using pyHeart. Linear regression analyses assessed the relationships of cardiac parameters with PFT and MRI-based lung volumes. Mean age was 56.3 ± 9.2 years (57% males). LV and right ventricular (RV) end-diastolic-, end-systolic-, stroke volume, LV peak ejection- and early/late diastolic filling rate were associated with FEV1, FVC, and residual volume (excluding late diastolic filling rate with FEV1, LV end-systolic/stroke volume and RV end-diastolic/end-systolic volumes with residual volume). In contrast, LV end-diastolic volume (ß = - 0.14, p = 0.01), early diastolic filling rate (ß = - 0.11, p = 0.04), and LV/RV stroke volume (ß = - 0.14, p = 0.01; ß = - 0.11, p = 0.01) were inversely associated with MRI-based lung volume. Subclinical cardiac impairment was associated with reduced FEV1, FVC, and residual volume. Cardiac parameters decreased with increasing MRI-based lung volume contrasting the results of PFT.
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http://dx.doi.org/10.1038/s41598-021-95655-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8352893PMC
August 2021

Variants associated with expression have sex-differential effects on lung function.

Wellcome Open Res 2020 24;5:111. Epub 2021 May 24.

Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, Western General Hospital, Edinburgh, EH4 2XU, UK.

Lung function is highly heritable and differs between the sexes throughout life. However, little is known about sex-differential genetic effects on lung function. We aimed to conduct the first genome-wide genotype-by-sex interaction study on lung function to identify genetic effects that differ between males and females. We tested for interactions between 7,745,864 variants and sex on spirometry-based measures of lung function in UK Biobank (N=303,612), and sought replication in 75,696 independent individuals from the SpiroMeta consortium. Five independent single-nucleotide polymorphisms (SNPs) showed genome-wide significant (P<5x10 ) interactions with sex on lung function, and 21 showed suggestive interactions (P<1x10 ). The strongest signal, from rs7697189 (chr4:145436894) on forced expiratory volume in 1 second (FEV ) (P=3.15x10 ), was replicated (P=0.016) in SpiroMeta. The C allele increased FEV more in males (untransformed FEV β=0.028 [SE 0.0022] litres) than females (β=0.009 [SE 0.0014] litres), and this effect was not accounted for by differential effects on height, smoking or pubertal age. rs7697189 resides upstream of the hedgehog-interacting protein ( ) gene and was previously associated with lung function and lung expression. We found expression was significantly different between the sexes (P=6.90x10 ), but we could not detect sex differential effects of rs7697189 on expression. We identified a novel genotype-by-sex interaction at a putative enhancer region upstream of the gene. Establishing the mechanism by which SNPs have different effects on lung function in males and females will be important for our understanding of lung health and diseases in both sexes.
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http://dx.doi.org/10.12688/wellcomeopenres.15846.2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7938335.2PMC
May 2021

Application of two job indices for general occupational demands in a pooled analysis of case-control studies on lung cancer.

Scand J Work Environ Health 2021 Sep 3;47(6):475-481. Epub 2021 May 3.

Jan Hovanec, IPA, Bürkle-de-la-Camp-Platz 1, 44789 Bochum, Germany.

Objectives: We investigated general job demands as a risk factor for lung cancer as well as their role in the association between occupational prestige and lung cancer.

Methods: In 13 case-control studies on lung cancer, as part of the international SYNERGY project, we applied indices for physical (PHI) and psychosocial (PSI) job demands - each with four categories (high to low). We estimated odds ratios (OR) and 95% confidence intervals (CI) for lung cancer by unconditional logistic regression, separately for men and women and adjusted for study centre, age, smoking behavior, and former employment in occupations with potential exposure to carcinogens. Further, we investigated, whether higher risks among men with low occupational prestige (Treiman's Standard International Occupational Prestige Scale) were affected by adjustment for the job indices.

Results: In 30 355 men and 7371 women, we found increased risks (OR) for lung cancer with high relative to low job demands in both men [PHI 1.74 (95% CI 1.56-1.93), PSI 1.33 (95% CI 1.17-1.51)] and women [PHI 1.62 (95% CI 1.24-2.11), PSI 1.31 (95% CI 1.09-1.56)]. OR for lung cancer among men with low occupational prestige were slightly reduced when adjusting for PHI [low versus high prestige OR from 1.44 (95% CI 1.32-1.58) to 1.30 (95% CI 1.17-1.45)], but not PSI.

Conclusions: Higher physical job demands were associated with increased risks of lung cancer, while associations for higher psychosocial demands were less strong. In contrast to physical demands, psychosocial demands did not contribute to clarify the association of occupational prestige and lung cancer.
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http://dx.doi.org/10.5271/sjweh.3967DOI Listing
September 2021

COVID-19 and heat waves: New challenges for healthcare systems.

Environ Res 2021 07 20;198:111153. Epub 2021 Apr 20.

Institute and Clinic for Occupational, Social and Environmental Medicine, University Hospital, LMU Munich, Ziemssenstr. 1, 80336, Munich, Germany; Comprehensive Pneumology Center Munich (CPC-M), Member of the German Center for Lung Research (DZL), Munich, Germany.

Heat waves and Covid-19 overlap, as this pandemic continues into summer 2021. Using a narrative review, we identified overlapping risk groups and propose coping strategies. The high-risk groups for heat-related health problems as well as for high-risk COVID-19 groups overlap considerably (elderly with pre-existing health conditions). Health care facilities will again be challenged by Covid-19 during heat waves. Health care personnel are also at risk of developing heat related health problems during hot periods due to the use of personal protective equipment to shield themselves from SARS-CoV-2 and must therefore be protected from excessive heat periods. Some existing recommendations for heat health protection contradict recommendations for COVID-19 protection. This paper provides a preliminary overview of possible strategies and interventions to tackle these ambiguities. The existing recommendations for protection against heat-related illnesses need revisions to determine whether they include essential aspects of infection control and occupational safety and how they may be supplemented.
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http://dx.doi.org/10.1016/j.envres.2021.111153DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8056477PMC
July 2021

Serum insulin is associated with right ventricle function parameters and lung volumes in subjects free of cardiovascular disease.

Eur J Endocrinol 2021 Feb;184(2):289-298

Department of Diagnostic and Interventional Radiology, Universitäts Klinikum Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.

Background: Diabetes mellitus is an established risk factor for cardiovascular diseases. Even impaired levels of glucose and insulin might harm organ function prior to diabetes onset. Whether serum glucose or insulin plays a direct role in cardiac dysfunction or lung volume reduction remains unclear. The aim was to investigate the relationship between glucose and insulin with the right ventricle and lung volumes within KORA-MRI FF4 study.

Methods: From the KORA-MRI FF4 cohort study 337 subjects (mean age 55.7 ± 9.1 years; 43% women) underwent a whole-body 3T MRI scan. Cardiac parameters derived from a cine-steady-state free precession sequence using cvi42. MRI-based lung volumes derived semi-automatically using an in-house algorithm. Fasting serum glucose, fasting insulin levels, and HOMA index were calculated in all study subjects. Linear regression analyses were performed to assess the relationships between glucose and insulin levels with right ventricle volumes and lung volumes adjusted for age, sex, BMI, and cardiovascular risk factors.

Results: In univariate and multivariate-adjusted models, high serum insulin was inversely associated with end-diastolic volume (β = -12.43, P < 0.001), end-systolic volume (β = -7.12, P < 0.001), stroke volume (β = -5.32, P < 0.001), but not with ejection fraction. The association remained significant after additional adjustment for lung volumes. Similarly, serum insulin was inversely associated with lung volume (β = -0.15, P = 0.04). Sensitivity analysis confirmed results after excluding subjects with known diabetes.

Conclusions: Serum insulin was inversely associated with right ventricle function and lung volumes in subjects from the general population free of cardiovascular disease, suggesting that increased insulin levels may contribute to subclinical cardiopulmonary circulation impairment.
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http://dx.doi.org/10.1530/EJE-20-1010DOI Listing
February 2021

Lung cancer risk in painters: results from the SYNERGY pooled case-control study consortium.

Occup Environ Med 2021 04 28;78(4):269-278. Epub 2020 Oct 28.

Stony Brook Cancer Center, Stony Brook University, Stony Brook, New York, USA.

Objectives: We evaluated the risk of lung cancer associated with ever working as a painter, duration of employment and type of painter by histological subtype as well as joint effects with smoking, within the SYNERGY project.

Methods: Data were pooled from 16 participating case-control studies conducted internationally. Detailed individual occupational and smoking histories were available for 19 369 lung cancer cases (684 ever employed as painters) and 23 674 age-matched and sex-matched controls (532 painters). Multivariable unconditional logistic regression models were adjusted for age, sex, centre, cigarette pack-years, time-since-smoking cessation and lifetime work in other jobs that entailed exposure to lung carcinogens.

Results: Ever having worked as a painter was associated with an increased risk of lung cancer in men (OR 1.30; 95% CI 1.13 to 1.50). The association was strongest for construction and repair painters and the risk was elevated for all histological subtypes, although more evident for small cell and squamous cell lung cancer than for adenocarcinoma and large cell carcinoma. There was evidence of interaction on the additive scale between smoking and employment as a painter (relative excess risk due to interaction >0).

Conclusions: Our results by type/industry of painter may aid future identification of causative agents or exposure scenarios to develop evidence-based practices for reducing harmful exposures in painters.
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http://dx.doi.org/10.1136/oemed-2020-106770DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7958079PMC
April 2021

Utilization and determinants of use of non-pharmacological interventions in COPD: Results of the COSYCONET cohort.

Respir Med 2020 09 12;171:106087. Epub 2020 Jul 12.

Institute of Health Economics and Health Care Management, Helmholtz Zentrum München, GmbH - German Research Center for Environmental Health, Comprehensive Pneumology Center Munich (CPC-M), Member of the German Center for Lung Research, Ingolstaedter Landstr. 1, 85764, Neuherberg, Germany; Institute for Medical Information Processing, Biometry and Epidemiology (IBE), Ludwig-Maximilians-University Munich (LMU), Marchioninistr. 15, 81377, Munich, Germany.

Background: Guidelines for chronic obstructive pulmonary disease (COPD) recommend supplementing pharmacotherapy with non-pharmacological interventions. Little is known about the use of such interventions by patients. We analyzed the utilization of a number of non-pharmacological interventions and identified potential determinants of use.

Methods: Based on self-reports, use of interventions (smoking cessation, influenza vaccination, physiotherapy, sports program, patient education, pulmonary rehabilitation) and recommendation to use were assessed in 1410 patients with COPD. The utilization was analyzed according to sex and severity of disease. Potential determinants of utilization included demographic variables and disease characteristics and were analyzed using logistic regression models.

Results: Influenza vaccination in the previous autumn/winter was reported by 73% of patients. About 19% were currently participating in a reimbursed sports program, 10% received physiotherapy, 38% were ever enrolled in an educational program, and 34% had ever participated in an outpatient or inpatient pulmonary rehabilitation program. Out of 553 current or former smokers, 24% had participated in a smoking cessation program. While reports of having received a recommendation to use mainly did not differ according to sex, women showed significantly (p < 0.05) higher utilization rates than men for all interventions except influenza vaccination. Smoking was a predictor for not having received a recommendation for utilization and also significantly associated with a reduced odds of utilization. We found a correlation between recommendation to use and utilization.

Conclusions: Utilization of non-pharmacological interventions was lower in men and smokers. A recommendation or offer to use by the physician could help to increase uptake.
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http://dx.doi.org/10.1016/j.rmed.2020.106087DOI Listing
September 2020

[Occupational medical pneumology - what's new?]

Dtsch Med Wochenschr 2020 08 13;145(16):1174-1178. Epub 2020 Aug 13.

Institut und Poliklinik für Arbeits-, Sozial- und Umweltmedizin LMU-Klinikum München.

In case of obstructive, interstitial and malignant respiratory and lung diseases, occupational causes must always be searched for. The sensitivity and specificity of specific IgE determinations in the diagnosis of occupational asthma are only slightly above 70 %, even for high-molecular allergens. If the patient's medical history is positive, further diagnostics must be carried out, if necessary up to specific exposure testing in specialised institutions. New data show that the serial FeNO determination after working days compared to days off contains additional information that can lead to a positive diagnostic classification. In case of interstitial lung diseases, (avoidable) occupational triggers must be searched for - a new questionnaire provides practical assistance. Patients with lung carcinoma should also be investigated for occupational causes. Here too, questionnaires and tables are available in simple language. In future lung cancer caused by long-term exposure to passive smoke will be considered an occupational disease.
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http://dx.doi.org/10.1055/a-1090-5723DOI Listing
August 2020

Accelerated epigenetic aging as a risk factor for chronic obstructive pulmonary disease and decreased lung function in two prospective cohort studies.

Aging (Albany NY) 2020 08 3;12(16):16539-16554. Epub 2020 Aug 3.

Center for Public Health and Environmental Assessment, US Environmental Protection Agency, Chapel Hill, NC 27709, USA.

Chronic obstructive pulmonary disease (COPD) is a frequent diagnosis in older individuals and contributor to global morbidity and mortality. Given the link between lung disease and aging, we need to understand how molecular indicators of aging relate to lung function and disease. Using data from the population-based KORA (Cooperative Health Research in the Region of Augsburg) surveys, we associated baseline epigenetic (DNA methylation) age acceleration with incident COPD and lung function. Models were adjusted for age, sex, smoking, height, weight, and baseline lung disease as appropriate. Associations were replicated in the Normative Aging Study. Of 770 KORA participants, 131 developed incident COPD over 7 years. Baseline accelerated epigenetic aging was significantly associated with incident COPD. The change in age acceleration (follow-up - baseline) was more strongly associated with COPD than baseline aging alone. The association between the change in age acceleration between baseline and follow-up and incident COPD replicated in the Normative Aging Study. Associations with spirometric lung function parameters were weaker than those with COPD, but a meta-analysis of both cohorts provide suggestive evidence of associations. Accelerated epigenetic aging, both baseline measures and changes over time, may be a risk factor for COPD and reduced lung function.
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http://dx.doi.org/10.18632/aging.103784DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7485704PMC
August 2020

Health-related quality of life associates with change in FEV in COPD: results from the COSYCONET cohort.

BMC Pulm Med 2020 May 29;20(1):148. Epub 2020 May 29.

Institute of Health Economics and Health Care Management, Helmholtz Zentrum München, GmbH - German Research Center for Environmental Health, Comprehensive Pneumology Center Munich (CPC-M), Member of the German Center for Lung Research (DZL), Ingolstaedter Landstr. 1, 85764, Neuherberg, Germany.

Background: Forced expiratory volume in one second (FEV) characterizes the pathophysiology of COPD and different trajectories of FEV decline have been observed in patients with COPD (e.g. gradual or episodic). There is limited information about the development of patient-reported health-related quality of life (HRQL) over the full range of the natural history of COPD. We examined the longitudinal association between change in FEV and change in disease-specific and generic HRQL.

Methods: We analysed data of 1734 patients with COPD participating in the COSYCONET cohort with up to 3 years of follow-up. Patients completed the Saint George's Respiratory Questionnaire (SGRQ) and the EQ-5D Visual Analog Scale (EQ VAS). Change score models were used to investigate the relationship between HRQL and FEV and to calculate mean changes in HRQL per FEV change categories [decrease (≤ - 100 ml), no change, increase (≥ 100 ml)] after 3 years. Applying hierarchical linear models (HLM), we estimated the cross-sectional between-subject difference and the longitudinal within-subject change of HRQL as related to a FEV difference or change.

Results: We observed a statistically significant deterioration in SGRQ (total score + 1.3 units) after 3 years, which was completely driven by the activity component (+ 4 units). No significant change was found for the generic EQ VAS. Over the same period, 58% of patients experienced a decrease in FEV, 28% were recorded as no change in FEV, and 13% experienced an increase. The relationship between HRQL and FEV was found to be approximately linear with decrease in FEV being statistically significantly associated with a deterioration in SGRQ (+ 3.20 units). Increase in FEV was associated with improvements in SGRQ (- 3.81 units). The associations between change in FEV and the EQ VAS were similar. Results of the HLMs were consistent and highly statistically significant, indicating cross-sectional and longitudinal associations. The largest estimates were found for the association between FEV and the SGRQ activity domain.

Conclusions: Difference and change in FEV over time correlate with difference and change in disease-specific and generic HRQL. We conclude, that deterioration of HRQL should induce timely re-examination of physical status and lung function and possibly reassessment of therapeutic regimes.

Trial Registration: NCT01245933. Date of registration: 18 November 2010.
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http://dx.doi.org/10.1186/s12890-020-1147-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7257512PMC
May 2020

Diesel Engine Exhaust Exposure, Smoking, and Lung Cancer Subtype Risks. A Pooled Exposure-Response Analysis of 14 Case-Control Studies.

Am J Respir Crit Care Med 2020 08;202(3):402-411

Cancer Epidemiology Unit, Department of Medical Sciences, University of Turin and ll Centro di Riferimento per l'Epidemiologia e la Prevenzione Oncologica in Piemonte (CPO-Piemonte), Torino, Italy.

Although the carcinogenicity of diesel engine exhaust has been demonstrated in multiple studies, little is known regarding exposure-response relationships associated with different exposure subgroups and different lung cancer subtypes. We expanded on a previous pooled case-control analysis on diesel engine exhaust and lung cancer by including three additional studies and quantitative exposure assessment to evaluate lung cancer and subtype risks associated with occupational exposure to diesel exhaust characterized by elemental carbon (EC) concentrations. We used a quantitative EC job-exposure matrix for exposure assessment. Unconditional logistic regression models were used to calculate lung cancer odds ratios and 95% confidence intervals (CIs) associated with various metrics of EC exposure. Lung cancer excess lifetime risks (ELR) were calculated using life tables accounting for all-cause mortality. Additional stratified analyses by smoking history and lung cancer subtypes were performed in men. Our study included 16,901 lung cancer cases and 20,965 control subjects. In men, exposure response between EC and lung cancer was observed: odds ratios ranged from 1.09 (95% CI, 1.00-1.18) to 1.41 (95% CI, 1.30-1.52) for the lowest and highest cumulative exposure groups, respectively. EC-exposed men had elevated risks in all lung cancer subtypes investigated; associations were strongest for squamous and small cell carcinomas and weaker for adenocarcinoma. EC lung cancer exposure response was observed in men regardless of smoking history, including in never-smokers. ELR associated with 45 years of EC exposure at 50, 20, and 1 μg/m were 3.0%, 0.99%, and 0.04%, respectively, for both sexes combined. We observed a consistent exposure-response relationship between EC exposure and lung cancer in men. Reduction of workplace EC levels to background environmental levels will further reduce lung cancer ELR in exposed workers.
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http://dx.doi.org/10.1164/rccm.201911-2101OCDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7465091PMC
August 2020

Respirable Crystalline Silica Exposure, Smoking, and Lung Cancer Subtype Risks. A Pooled Analysis of Case-Control Studies.

Am J Respir Crit Care Med 2020 08;202(3):412-421

The M. Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland.

Millions of workers around the world are exposed to respirable crystalline silica. Although silica is a confirmed human lung carcinogen, little is known regarding the cancer risks associated with low levels of exposure and risks by cancer subtype. However, little is known regarding the disease risks associated with low levels of exposure and risks by cancer subtype. We aimed to address current knowledge gaps in lung cancer risks associated with low levels of occupational silica exposure and the joint effects of smoking and silica exposure on lung cancer risks. Subjects from 14 case-control studies from Europe and Canada with detailed smoking and occupational histories were pooled. A quantitative job-exposure matrix was used to estimate silica exposure by occupation, time period, and geographical region. Logistic regression models were used to estimate exposure-disease associations and the joint effects of silica exposure and smoking on risk of lung cancer. Stratified analyses by smoking history and cancer subtypes were also performed. Our study included 16,901 cases and 20,965 control subjects. Lung cancer odds ratios ranged from 1.15 (95% confidence interval, 1.04-1.27) to 1.45 (95% confidence interval, 1.31-1.60) for groups with the lowest and highest cumulative exposure, respectively. Increasing cumulative silica exposure was associated ( trend < 0.01) with increasing lung cancer risks in nonsilicotics and in current, former, and never-smokers. Increasing exposure was also associated ( trend ≤ 0.01) with increasing risks of lung adenocarcinoma, squamous cell carcinoma, and small cell carcinoma. Supermultiplicative interaction of silica exposure and smoking was observed on overall lung cancer risks; superadditive effects were observed in risks of lung cancer and all three included subtypes. Silica exposure is associated with lung cancer at low exposure levels. An exposure-response relationship was robust and present regardless of smoking, silicosis status, and cancer subtype.
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http://dx.doi.org/10.1164/rccm.201910-1926OCDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7465090PMC
August 2020

[Occurrence of bronchial asthma and age at initial asthma diagnosis-first results of the German National Cohort].

Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz 2020 Apr;63(4):397-403

Abteilung Epidemiologie von Krebserkrankungen, Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, Deutschland.

Background: Asthma is one of the most common chronic diseases in both children and adults. Asthma first occurring in adulthood (adult-onset asthma, AOA) is associated with poorer prognosis compared to childhood-onset asthma (COA), which urgently calls for more research in this area. The aim of this work was to analyze the data on asthma collected in the German National Cohort and compare it with the German Health Interview and Examination Survey for Adults (DEGS), in particular regarding AOA.

Material And Methods: Our analysis was based on the dataset of the main questionnaire at mid-term of the German National Cohort baseline examination, comprising 101,723 participants. Variables considered in the analyses were self-reported diagnosis of asthma, age at first diagnosis, asthma treatment in the past 12 months, age, and sex.

Results: In the midterm dataset, 8.7% of women and 7.0% of men in the German National Cohort reported that they had ever been diagnosed with asthma. Approximately one third of participants with asthma received their initial diagnosis before their 18th birthday. COA affected 2.2% of women and 2.8% of men, whereas AOA affected 6.5% of women and 4.2% of men. During the previous 12 months, 33% of COA cases and 60% of AOA cases were medically treated.

Conclusion: The proportion of persons affected by asthma in the German National Cohort, as well as observed patterns regarding age and gender, corresponds to other data sources such as DEGS. However, in our analysis, the proportion of individuals with AOA was higher than described in the literature. The increase in cumulative asthma diagnoses with age is markedly steeper in younger participants, indicating a rising trend over time.
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http://dx.doi.org/10.1007/s00103-020-03105-yDOI Listing
April 2020

[Lung function in the German National Cohort: methods and initial results].

Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz 2020 Mar;63(3):322-331

Abteilung Epidemiologie von Krebserkrankungen, DKFZ Heidelberg, Heidelberg, Deutschland.

Background: A nationwide assessment of the respiratory status on the basis of standardized lung function measurements has so far not been available in Germany. The present work describes the lung function tests in the German National Cohort (GNC) and presents initial results based on the GNC Midterm Baseline Dataset.

Material And Methods: The assessment of lung function in the GNC comprised spirometry (level 1) and the determination of exhaled nitric oxide (FeNO, level 2). Our quality assurance concept included regular training of lung function test procedures at various GNC sites, interim evaluations of test quality, as well as regular calibration/measurement checks of test equipment. For spirometry, we established a stepwise procedure for offline quality control based on raw flow volume curves.

Results: In the present dataset (n = 101,734), spirometry was available for 86,893 study participants and FeNO was available for 15,228 participants. The average (±SD) FEV Z score (according to GLI 2012) was -0.321 ± 1.047, the FVC Z score was -0.153 ± 0.941, and the FEV/FVC Z score was -0.337 ± 0.901. The difference in FEV/FVC between current smokers and never-smokers increased with age. The average FeNO was 14.2 ÷ 2.0 ppb. Current smoking reduced FeNO levels by 43%, whereas respiratory allergy increased FeNO levels by 16% in nonsmokers.

Discussion: The results of spirometry and the FeNO measurements are in the expected range with regard to their distributions and correlates. The GNC provides a valuable basis for future investigations of respiratory health and its determinants as well as research into the prevention of respiratory diseases in Germany.
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http://dx.doi.org/10.1007/s00103-020-03102-1DOI Listing
March 2020

Review of the characteristics and possible health effects of particles emitted from laser printing devices.

Indoor Air 2020 05 3;30(3):396-421. Epub 2020 Feb 3.

Department of Material Analysis and Indoor Chemistry, Fraunhofer WKI, Braunschweig, Germany.

Many studies have shown that the use of laser printing devices (LPDs) contributes to the release of particles into the indoor environment. However, after more than two decades of research, the physicochemical properties of LPD-emitted particles and the possible health effects from exposure to particles are still heavily debated. We therefore carried out a critical review of the published studies around emissions and health effects of LPD-emitted particles, aiming at elucidating the nature of these particles and their potential health risks. Realizing the varying methodologies of the studies, a classification of the reviewed studies is adopted, resulting in three categories of emission studies (chamber experiment, office/room measurement, and photocopy shop measurement), and three types of health studies (in vitro/animal studies, human studies in the real world, and human studies in controlled settings). The strengths and limitations of each type of study are discussed in-depth, which in turn helps to understand the cause of divergent results. Overall, LPD-emitted particles are mainly condensed or secondary-formed semi-volatile organic compounds (SVOCs), while solid toner particles account for a very small fraction. The health risk from exposure to LPD-emitted particles is small compared with the health risk from exposure to ambient particles.
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http://dx.doi.org/10.1111/ina.12646DOI Listing
May 2020

Determinants of healthcare utilization and costs in COPD patients: first longitudinal results from the German COPD cohort COSYCONET.

Int J Chron Obstruct Pulmon Dis 2019 5;14:1423-1439. Epub 2019 Jul 5.

Institute of Health Economics and Health Care Management, Helmholtz Zentrum München, GmbH - German Research Center for Environmental Health, Comprehensive Pneumology Center Munich (CPC-M), Member of the German Center for Lung Research , 85764 Neuherberg, Germany.

Background: In light of overall increasing healthcare expenditures, it is mandatory to study determinants of future costs in chronic diseases. This study reports the first longitudinal results on healthcare utilization and associated costs from the German chronic obstructive pulmonary disease (COPD) cohort COSYCONET.

Material And Methods: Based on self-reported data of 1904 patients with COPD who attended the baseline and 18-month follow-up visits, direct costs were calculated for the 12 months preceding both examinations. Direct costs at follow-up were regressed on baseline disease severity and other co-variables to identify determinants of future costs. Change score models were developed to identify predictors of cost increases over 18 months. As possible predictors, models included GOLD grade, age, sex, education, smoking status, body mass index, comorbidity, years since COPD diagnosis, presence of symptoms, and exacerbation history.

Results: Inflation-adjusted mean annual direct costs increased by 5% (n.s., €6,739 to €7,091) between the two visits. Annual future costs were significantly higher in baseline GOLD grades 2, 3, and 4 (factors 1.24, 95%-confidence interval [1.07-1.43], 1.27 [1.09-1.48], 1.57 [1.27-1.93]). A history of moderate or severe exacerbations within 12 months, a comorbidity count >3, and the presence of dyspnea and underweight were significant predictors of cost increase (estimates ranging between + €887 and + €3,679, all <0.05).

Conclusions: Higher GOLD grade, comorbidity burden, dyspnea and moderate or severe exacerbations were determinants of elevated future costs and cost increases in COPD. In addition we identified underweight as independent risk factor for an increase in direct healthcare costs over time.
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http://dx.doi.org/10.2147/COPD.S201899DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6616193PMC
February 2020

Metabolomics Identifies Novel Blood Biomarkers of Pulmonary Function and COPD in the General Population.

Metabolites 2019 Apr 1;9(4). Epub 2019 Apr 1.

Epidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, NC 27709, USA.

Determination of metabolomic signatures of pulmonary function and chronic obstructive pulmonary disease (COPD) in the general population could aid in identification and understanding of early disease processes. Metabolome measurements were performed on serum from 4742 individuals (2354 African-Americans and 1529 European-Americans from the Atherosclerosis Risk in Communities study and 859 Europeans from the Cooperative Health Research in the Region of Augsburg study). We examined 368 metabolites in relation to cross-sectional measures of forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), their ratio (FEV1/FVC) and COPD using multivariable regression followed by meta-analysis. At a false discovery rate of 0.05, 95 metabolites were associated with FEV1 and 100 with FVC (73 overlapping), including inverse associations with branched-chain amino acids and positive associations with glutamine. Ten metabolites were associated with FEV1/FVC and seventeen with COPD (393 cases). Enriched pathways of amino acid metabolism were identified. Associations with FEV1 and FVC were not driven by individuals with COPD. We identified novel metabolic signatures of pulmonary function and COPD in African and European ancestry populations. These may allow development of biomarkers in the general population of early disease pathogenesis, before pulmonary function has decreased to levels diagnostic for COPD.
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http://dx.doi.org/10.3390/metabo9040061DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6523962PMC
April 2019

New genetic signals for lung function highlight pathways and chronic obstructive pulmonary disease associations across multiple ancestries.

Nat Genet 2019 03 25;51(3):481-493. Epub 2019 Feb 25.

Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.

Reduced lung function predicts mortality and is key to the diagnosis of chronic obstructive pulmonary disease (COPD). In a genome-wide association study in 400,102 individuals of European ancestry, we define 279 lung function signals, 139 of which are new. In combination, these variants strongly predict COPD in independent populations. Furthermore, the combined effect of these variants showed generalizability across smokers and never smokers, and across ancestral groups. We highlight biological pathways, known and potential drug targets for COPD and, in phenome-wide association studies, autoimmune-related and other pleiotropic effects of lung function-associated variants. This new genetic evidence has potential to improve future preventive and therapeutic strategies for COPD.
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http://dx.doi.org/10.1038/s41588-018-0321-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6397078PMC
March 2019

Metastable DNA methylation sites associated with longitudinal lung function decline and aging in humans: an epigenome-wide study in the NAS and KORA cohorts.

Epigenetics 2018 21;13(10-11):1039-1055. Epub 2018 Oct 21.

c Office of Research , Dana-Farber/Harvard Cancer Institute , Boston , MA , USA.

DNA methylation is an epigenetic regulator of gene transcription, which has been found to be both metastable and variable within human cohort studies. Currently, few studies have been done to identify metastable DNA methylation biomarkers associated with longitudinal lung function decline in humans. The identification of such biomarkers is important for screening vulnerable populations. We hypothesized that quantifiable blood-based DNA methylation alterations would serve as metastable biomarkers of lung function decline and aging, which may help to discover new pathways and/or mechanisms related to pulmonary pathogenesis. Using linear mixed models, we performed an Epigenome Wide Association Study (EWAS) between DNA methylation at CpG dinucleotides and longitudinal lung function (FVC, FEV, FEF) decline and aging with initial discovery in the Normative Aging Study, and replication in the Cooperative Health Research in the Region of Augsburg cohort. We identified two metastable epigenetic loci associated with either poor lung function and aging, cg05575921 (AHRR gene), or lung function independently of aging, cg06126421 (IER3 gene). These loci may inform basic mechanisms associated with pulmonary function, pathogenesis, and aging. Human epigenomic variation, may help explain features of lung function decline and related pathophysiology not attributable to DNA sequence alone, such as accelerated pulmonary decline in smokers, former smokers, and perhaps non-smokers. Our EWAS across two cohorts, therefore, will likely have implications for the human population, not just the elderly.
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http://dx.doi.org/10.1080/15592294.2018.1529849DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6342072PMC
March 2019

Meta-analysis of exome array data identifies six novel genetic loci for lung function.

Wellcome Open Res 2018 12;3. Epub 2018 Jan 12.

Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, NC 27514, USA.

Over 90 regions of the genome have been associated with lung function to date, many of which have also been implicated in chronic obstructive pulmonary disease. We carried out meta-analyses of exome array data and three lung function measures: forced expiratory volume in one second (FEV ), forced vital capacity (FVC) and the ratio of FEV to FVC (FEV /FVC). These analyses by the SpiroMeta and CHARGE consortia included 60,749 individuals of European ancestry from 23 studies, and 7,721 individuals of African Ancestry from 5 studies in the discovery stage, with follow-up in up to 111,556 independent individuals. We identified significant (P<2·8x10 ) associations with six SNPs: a nonsynonymous variant in , which is predicted to be damaging, three intronic SNPs ( and ) and two intergenic SNPs near to and Expression quantitative trait loci analyses found evidence for regulation of gene expression at three signals and implicated several genes, including and . Further interrogation of these loci could provide greater understanding of the determinants of lung function and pulmonary disease.
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http://dx.doi.org/10.12688/wellcomeopenres.12583.3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6081985PMC
January 2018

Automated MR-based lung volume segmentation in population-based whole-body MR imaging: correlation with clinical characteristics, pulmonary function testing and obstructive lung disease.

Eur Radiol 2019 Mar 27;29(3):1595-1606. Epub 2018 Aug 27.

Department of Diagnostic and Interventional Radiology, University Hospital Heidelberg, Im Neuenheimer Feld 110, 69120, Heidelberg, Germany.

Objectives: Whole-body MR imaging is increasingly utilised; although for lung dedicated sequences are often not included, the chest is typically imaged. Our objective was to determine the clinical utility of lung volumes derived from non-dedicated MRI sequences in the population-based KORA-FF4 cohort study.

Methods: 400 subjects (56.4 ± 9.2 years, 57.6% males) underwent whole-body MRI including a coronal T1-DIXON-VIBE sequence in inspiration breath-hold, originally acquired for fat quantification. Based on MRI, lung volumes were derived using an automated framework and related to common predictors, pulmonary function tests (PFT; spirometry and pulmonary gas exchange, n = 214) and obstructive lung disease.

Results: MRI-based lung volume was 4.0 ± 1.1 L, which was 64.8 ± 14.9% of predicted total lung capacity (TLC) and 124.4 ± 27.9% of functional residual capacity. In multivariate analysis, it was positively associated with age, male, current smoking and height. Among PFT indices, MRI-based lung volume correlated best with TLC, alveolar volume and residual volume (RV; r = 0.57 each), while it was negatively correlated to FEV/FVC (r = 0.36) and transfer factor for carbon monoxide (r = 0.16). Combining the strongest PFT parameters, RV and FEV/FVC remained independently and incrementally associated with MRI-based lung volume (β = 0.50, p = 0.04 and β = - 0.02, p = 0.02, respectively) explaining 32% of the variability. For the identification of subjects with obstructive lung disease, height-indexed MRI-based lung volume yielded an AUC of 0.673-0.654.

Conclusion: Lung volume derived from non-dedicated whole-body MRI is independently associated with RV and FEV/FVC. Furthermore, its moderate accuracy for obstructive lung disease indicates that it may be a promising tool to assess pulmonary health in whole-body imaging when PFT is not available.

Key Points: • Although whole-body MRI often does not include dedicated lung sequences, lung volume can be automatically derived using dedicated segmentation algorithms • Lung volume derived from whole-body MRI correlates with typical predictors and risk factors of respiratory function including smoking and represents about 65% of total lung capacity and 125% of the functional residual capacity • Lung volume derived from whole-body MRI is independently associated with residual volume and the ratio of forced expiratory volume in 1 s to forced vital capacity and may allow detection of obstructive lung disease.
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http://dx.doi.org/10.1007/s00330-018-5659-9DOI Listing
March 2019

Association of generic health-related quality of life (EQ-5D dimensions) and inactivity with lung function in lung-healthy German adults: results from the KORA studies F4L and Age.

Qual Life Res 2018 Mar 6;27(3):735-745. Epub 2018 Feb 6.

Institute of Epidemiology I, Helmholtz Zentrum München - German Research Center for Environmental Health, Ingolstädter Landstr. 1, 85764, Neuherberg, Germany.

Purpose: Among patients with lung disease, decreased lung function is associated with lower health-related quality of life. However, whether this association is detectable within the physiological variability of respiratory function in lung-healthy populations is unknown. We analyzed the association of each EQ-5D-3L dimension (mobility, self-care, usual activities, pain/discomfort, anxiety/depression) and self-reported physical inactivity with spirometric indices in lung-healthy adults. Modulating effects between inactivity and EQ-5D dimensions were considered.

Methods: 1132 non-smoking, apparently lung-healthy participants (48% male, aged 64 ± 12 years) from the population-based KORA F4L and Age surveys in Southern Germany were analyzed. Associations of each EQ-5D dimension and inactivity with spirometric indices serving as outcomes (forced expiratory volume in 1 s (FEV), forced vital capacity (FVC), FEV/FVC, and mid-expiratory flow) were examined by linear regression, considering possible confounders. Interactions between EQ-5D dimensions (no problems/any problems) and inactivity (four categories of time spent engaging in exercise: inactive to most active) were assessed.

Results: Among all participants 42% reported no problems in any EQ-5D dimension, 24% were inactive and 32% exercised > 2 h/week. After adjustment, FEV was - 99 ml (95% CI - 166; - 32) and FVC was - 109 ml (95% CI - 195; - 24) lower among subjects with mobility problems. Comparable estimates were observed for usual activities. Inactivity was negatively associated with FVC (β-coefficient: - 83 ml, 95% CI - 166; 0), but showed no interactions with EQ-5D.

Conclusions: Problems with mobility or usual activities, and inactivity were associated with slightly lower spirometric parameters in lung-healthy adults, suggesting a relationship between perceived physical functioning and volumetric lung function.
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http://dx.doi.org/10.1007/s11136-017-1763-6DOI Listing
March 2018

Heterogeneous pattern of differences in respiratory parameters between elderly with either good or poor FEV.

BMC Pulm Med 2018 Feb 6;18(1):27. Epub 2018 Feb 6.

Institute of Epidemiology I, Helmholtz Zentrum München - German Research Center for Environmental Health, Ingolstaedter Landstrasse 1, D-85764, Neuherberg, Germany.

Background: The relationship of spirometric values to other respiratory and functional parameters in advanced age is not well studied. We assessed this relationship in elderly subjects with either good or poor spirometric parameters to reveal whether different domains of lung function show comparable differences between the two groups.

Methods: Among subjects of the population-based KORA-Age cohort (n = 935, 65-90y; 51% male) two groups were selected from either the lower (LED; n = 51) or the upper (UED; n = 72) end of the FEV distribution. All subjects did not have a history of lung disease and were non-smokers at the time of the study. Measurements included spirometry, body plethysmography, diffusing capacity for NO and CO, respiratory pump function and exhaled NO (FeNO). In addition, 6-min walking distance as a functional overall measure, as well as telomere length of blood leukocytes and serum 8-hydroxydeoxyguanosine (8-OHdG) as potential markers of overall biological ageing and stress were determined.

Results: In the majority of parameters, LED subjects showed significantly impaired values compared to UED subjects. Differences in spirometric parameters, airway resistance and respiratory pump function ranged between 10% and more than 90% in terms of predicted values. In contrast, volume-related CO and NO diffusing capacity showed differences between groups of lower than 5%, while telomere length, 8-OHdG and FeNO were similar. This was reflected in the differences in "functional age" as derived from prediction equations.

Conclusions: In elderly subjects without a history of lung disease differences in spirometric parameters were associated with differences in other lung-mechanical parameters including body plethysmography but not with differences in volume-corrected gas exchange measures. Thus, the concept of a general "lung age" as suggested by the widespread use of this term in connection with spirometry should be considered with caution.
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http://dx.doi.org/10.1186/s12890-018-0582-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5801692PMC
February 2018

Association of physical activity with lung function in lung-healthy German adults: results from the KORA FF4 study.

BMC Pulm Med 2017 Dec 28;17(1):215. Epub 2017 Dec 28.

Institute of Epidemiology I, Helmholtz Zentrum München - German Research Center for Environmental Health, Ingolstädter Landstr. 1, 85764, Neuherberg, Germany.

Background: In lung disease, physical activity (PA) yields beneficial health effects, but its association with the function of healthy lungs has rarely been studied. We investigated the association of accelerometer-based PA with spirometric indices, maximal inspiratory mouth pressure (PI) and lung diffusion capacity in lung-healthy adults.

Methods: In total, 341 apparently lung-healthy participants from the population-based KORA (Cooperative Health Research in the Region of Augsburg) FF4 cohort study (45% male, aged 48-68 years, 47% never smokers) completed lung function testing and wore ActiGraph accelerometers over a one week period at the hip. In adjusted regression analyses, moderate to vigorous PA (MVPA) was characterized as: sex-specific activity quartiles, achieving ≥ 10 consecutive minutes (yes vs. no), and meeting the WHO PA recommendations (yes vs. no).

Results: Positive associations of MVPA-quartiles with forced expiratory volume in 1 s (FEV), forced vital capacity (FVC), and corresponding Global Lung Function Initiative z-scores were found. Subjects in the most active quartile (> 47 or > 50 min/day for females and males, respectively) had 142 ml [95% CI: 23, 260] higher FEV and 155 ml [95% CI: 10, 301] higher FVC than those in the least active quartile (< 17 or < 21 min/day for females and males, respectively); however these associations were stronger among ex-/current smokers. Achieving at least once 10 consecutive minutes of MVPA was only associated with higher PI [β-estimate: 0.57 kPa; 95% CI: 0.04, 1.10], remaining significant among never smokers. No associations were found with diffusion capacity or for reaching the WHO-recommended 150 min of MVPA/week in 10-min bouts.

Conclusions: Although the effects were small, active subjects showed higher spirometric results. The observed associations were more pronounced among ever smokers suggesting a higher benefit of PA for subjects being at a higher risk for chronic lung diseases.
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http://dx.doi.org/10.1186/s12890-017-0562-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5745968PMC
December 2017

The contribution of symptoms and comorbidities to the economic impact of COPD: an analysis of the German COSYCONET cohort.

Int J Chron Obstruct Pulmon Dis 2017 4;12:3437-3448. Epub 2017 Dec 4.

Institute of Health Economics and Health Care Management, Helmholtz Zentrum München GmbH, German Research Center for Environmental Health, Comprehensive Pneumology Center Munich (CPC-M), Member of the German Center for Lung Research, Neuherberg.

Background: Although patients with COPD often have various comorbidities and symptoms, limited data are available on the contribution of these aspects to health care costs. This study analyzes the association of frequent comorbidities and common symptoms with the annual direct and indirect costs of patients with COPD.

Methods: Self-reported information on 33 potential comorbidities and symptoms (dyspnea, cough, and sputum) of 2,139 participants from the baseline examination of the German COPD cohort COSYCONET was used. Direct and indirect costs were calculated based on self-reported health care utilization, work absence, and retirement. The association of comorbidities, symptoms, and COPD stage with annual direct/indirect costs was assessed by generalized linear regression models. Additional models analyzed possible interactions between COPD stage, the number of comorbidities, and dyspnea.

Results: Unadjusted mean annual direct costs were €7,263 per patient. Other than COPD stage, a high level of dyspnea showed the strongest driving effect on direct costs (+33%). Among the comorbidities, osteoporosis (+38%), psychiatric disorders (+36%), heart disease (+25%), cancer (+24%), and sleep apnea (+21%) were associated with the largest increase in direct costs (<0.01). A sub-additive interaction between advanced COPD stage and a high number of comorbidities reduced the independent cost-driving effects of these factors. For indirect costs, besides dyspnea (+34%), only psychiatric disorders (+32%) and age (+62% per 10 years) were identified as significant drivers of costs (<0.04). In the subsequent interaction analysis, a high number of comorbidities was found to be a more crucial factor for increased indirect costs than single comorbidities.

Conclusion: Detailed knowledge about comorbidities in COPD is useful not only for clinical purposes but also to identify relevant cost factors and their interactions and to establish a ranking of major cost drivers. This could help in focusing therapeutic efforts on both clinically and economically important comorbidities in COPD.
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http://dx.doi.org/10.2147/COPD.S141852DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5720349PMC
September 2018

Shared genetic origin of asthma, hay fever and eczema elucidates allergic disease biology.

Nat Genet 2017 Dec 30;49(12):1752-1757. Epub 2017 Oct 30.

Melbourne School of Population and Global Health, University of Melbourne, Melbourne, Victoria, Australia.

Asthma, hay fever (or allergic rhinitis) and eczema (or atopic dermatitis) often coexist in the same individuals, partly because of a shared genetic origin. To identify shared risk variants, we performed a genome-wide association study (GWAS; n = 360,838) of a broad allergic disease phenotype that considers the presence of any one of these three diseases. We identified 136 independent risk variants (P < 3 × 10), including 73 not previously reported, which implicate 132 nearby genes in allergic disease pathophysiology. Disease-specific effects were detected for only six variants, confirming that most represent shared risk factors. Tissue-specific heritability and biological process enrichment analyses suggest that shared risk variants influence lymphocyte-mediated immunity. Six target genes provide an opportunity for drug repositioning, while for 36 genes CpG methylation was found to influence transcription independently of genetic effects. Asthma, hay fever and eczema partly coexist because they share many genetic risk variants that dysregulate the expression of immune-related genes.
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http://dx.doi.org/10.1038/ng.3985DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5989923PMC
December 2017

The longitudinal relationship of work stress with peak expiratory flow: a cohort study.

Int Arch Occup Environ Health 2017 10 29;90(7):695-701. Epub 2017 May 29.

Institute for Medical Sociology, Centre for Health and Society, Faculty of Medicine, University of Düsseldorf, Düsseldorf, Germany.

Purpose: Research has suggested that psychological stress is associated with reduced lung function and with the development of respiratory disease. Among the major potential sources of stress in adulthood are working conditions. We aimed to examine the relationship of work stress with lung function.

Methods: We drew on 4-year prospective data from the Survey of Health, Ageing and Retirement in Europe. The analyzed sample comprised 2627 workers aged 50 years or older who were anamnestically free of respiratory disease. Work stress at baseline was operationalized by abbreviated instruments measuring the well-established effort-reward imbalance model (seven items) and the control component of the job-demand control (two items). Peak expiratory flow (PEF) was determined at baseline and at follow-up. Continuous and categorized (i.e., by the tertile) work stress variables were employed in multivariable linear regression models to predict PEF change.

Results: Work stress did not show statistically significant associations with PEF change. For instance, the unstandardized regression coefficient for PEF decline according to high versus low effort-reward imbalance was -1.41 (95% confidence interval = -3.75, 0.94).

Conclusions: Our study is the first to examine prospective relationships between work stress and PEF. Overall, we did not observe meaningful associations. Future studies should consider a broader spectrum of spirometric parameters and should expand research to younger and possibly less-selected working populations (i.e., aged <50 years).
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http://dx.doi.org/10.1007/s00420-017-1232-0DOI Listing
October 2017

Relationship of hyperlipidemia to comorbidities and lung function in COPD: Results of the COSYCONET cohort.

PLoS One 2017 15;12(5):e0177501. Epub 2017 May 15.

Institute and Outpatient Clinic for Occupational, Social and Environmental Medicine, Ludwig-Maximilians-Universität München, Munich, Germany.

Although hyperlipidemia is common in COPD, its relationship to comorbidities, risk factors and lung function in COPD has not been studied in detail. Using the baseline data of the COSYCONET cohort we addressed this question. Data from 1746 COPD patients (GOLD stage 1-4; mean age 64.6 y, mean FEV1%pred 57%) were evaluated, focusing on the comorbidities hyperlipidemia, diabetes and cardiovascular complex (CVC; including arterial hypertension, cardiac failure, ischemic heart disease). Risk factors comprised age, gender, BMI, and packyears of smoking. The results of linear and logistic regression analyses were implemented into a path analysis model describing the multiple relationships between parameters. Hyperlipidemia (prevalence 42.9%) was associated with lower intrathoracic gas volume (ITGV) and higher forced expiratory volume in 1 second (FEV1) when adjusting for its multiple relationships to risk factors and other comorbidities. These findings were robust in various statistical analyses. The associations between comorbidities and risk factors were in accordance with previous findings, thereby underlining the validity of our data. In conclusion, hyperlipidemia was associated with less hyperinflation and airway obstruction in patients with COPD. This surprising result might be due to different COPD phenotypes in these patients or related to effects of medication.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0177501PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5432186PMC
September 2017

Costs and health-related quality of life in Alpha-1-Antitrypsin Deficient COPD patients.

Respir Res 2017 04 17;18(1):60. Epub 2017 Apr 17.

Institute of Health Economics and Health Care Management, Helmholtz Zentrum München, GmbH, German Research Center for Environmental Health, Comprehensive Pneumology Center Munich (CPC-M), Member of the German Center for Lung Research, Ingolstaedter Landstr. 1, 85764, Neuherberg, Germany.

Background: Alpha-1-Antitrypsin Deficiency (AATD) is an economically unexplored genetic disease.

Methods: Direct and indirect costs (based on self-reported information on healthcare utilization) and health-related quality of life (HRQL, as assessed by SGRQ, CAT, and EQ-5D-3 L) were compared between 131 AATD patients (106 with, 25 without augmentation therapy (AT)) and 2,049 COPD patients without AATD participating in the COSYCONET COPD cohort. The medication costs of AT were excluded from all analyses to reveal differences associated with morbidity profiles. The association of AATD (with/without AT) with costs or HRQL was examined using generalized linear regression modelling (GLM) adjusting for age, sex, GOLD grade, BMI, smoking status, education and comorbidities.

Results: Adjusted mean direct annual costs were €6,099 in AATD patients without AT, €7,117 in AATD patients with AT (excluding costs for AT), and €7,460 in COPD patients without AATD. AATD with AT was significantly associated with higher outpatient (+273%) but lower inpatient (-35%) and medication costs (-10%, disregarding AT) compared with COPD patients without AATD. There were no significant differences between groups regarding indirect costs and HRQL.

Conclusion: Apart from AT costs, AATD patients tended to have lower, though not significant, overall costs and similar HRQL compared to COPD patients without AATD. AT was not associated with lower costs or higher HRQL.

Trial Registration: NCT01245933.
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http://dx.doi.org/10.1186/s12931-017-0543-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5392996PMC
April 2017
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