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The Gravity Recovery Object Oriented Programming System (GROOPS) is a software package written in C++ that enables the user to perform core geodetic tasks. The software features gravity field recovery from satellite and terrestrial data, the determination of low-earth-orbiting satellite orbits from global navigation satellite system (GNSS) measurements, and the computation of GNSS constellations and ground station networks. For an easy and intuitive setup of complex workflows, GROOPS contains a graphical user interface to create and edit configuration files. The source code of GROOPS is released under the GPL v3 license and is available on GitHub (https://github.com/groops-devs/groops) together with documentation, a cookbook with guided examples, and installation instructions for different platforms. In this contribution we give a software overview and present results of different applications and data sets computed with GROOPS.

Background Cardiopulmonary exercise testing allows for assessment of cardiac and respiratory limitation, but is often affected by patient effort. Indices of oxygen kinetics, including the oxygen uptake efficiency slope (OUES), oxygen uptake–work-rate slope (VO 2 –WR slope) and the heart rate–oxygen uptake slope (HR–VO 2 slope) are relatively effort independent but may be affected by patient characteristics. The objective of this study is to identify the impact of factors, such as age, gender, body size, respiratory function, smoking and beta-blockade on these parameters, as well as generate predictive equations. Methods 1708 volunteers from the population-based Study of Health in Pomerania underwent an incremental bicycle exercise protocol. Markers of oxygen kinetics were calculated. Participants with structural heart disease, echocardiographic or lung function pathology were excluded, leaving 577 males and 625 females. Age, height, weight, smoking, forced expiratory volume in 1s (FEV 1 ) and beta-blockers were analysed for their influencing power by gender. Quantile regression analysis determined the reference equations for each parameter. Results Age, gender, height, weight and FEV 1 (but not percent predicted FEV 1 ) are strongly related to OUES. Participants using beta-blockers and male smokers had significantly lower OUES values. VO 2 –WR slope was minimally affected by age, gender, weight and FEV 1 . Gender, height, weight and beta-blocker use, but not FEV 1 and smoking status, were related to the HR–VO 2 slope whilst age was only related in females. Conclusions Markers of oxygen kinetics are differentially affected by patient characteristics. This study provides normal reference values for these variables thereby facilitating interpretation of oxygen uptake kinetics in health and disease.

Objective To assess the agreement of sleep parameters measured by two actigraphs (SOMNOwatch plus ® , ActiGraph GT3X+ ® ) at two different placements (wrist, hip) and of self-reported sleep with polysomnography (PSG). Methods We estimated agreement with PSG for total sleep time (TST), sleep onset latency (SOL), wake after sleep onset (WASO), number of awakenings after sleep onset (NASO), and sleep efficiency (SE%) for 100 participants of the general population, aged 18–75 years by judging mean differences to PSG and intervals of agreement using Bland–Altman plots. Results Mean difference to PSG for TST was 8.3 min (95% confidence intervals [CI] −7.4; 24.1) for SOMNOwatch plus ® (wrist), 39.8 min (95% CI 24.3; 55.3) for self-report, −79.0 min (95% CI −89.0; −68.9) for SOMNOwatch plus ® (hip), and −81.1 min (95% CI −91.9; −70.4) for GT3X+ ® (hip), respectively. The width of intervals of agreement differed with the placement of the devices. Mean differences to PSG were higher for hip-based measurements compared with wrist placement for most parameters. Conclusions Agreement of sleep parameters assessed by actigraphy with PSG differs with the placement of the device and is limited for hip-based measurements. Agreement of self-report with PSG is comparable to that of actigraphy for some parameters.

Forced vital capacity (FVC), a spirometric measure of pulmonary function, reflects lung volume and is used to diagnose and monitor lung diseases. We performed genome-wide association study meta-analysis of FVC in 52,253 individuals from 26 studies and followed up the top associations in 32,917 additional individuals of European ancestry. We found six new regions associated at genome-wide significance (P

The lung constantly interacts with numerous pathogens. Thus, complex local immune defence mechanisms are essential to recognise and dispose of these intruders. This work describes the detection, characterisation and three-dimensional structure of a novel protein of the lung (surfactant-associated protein 3 (SFTA3/SP-H)) with putative immunological features. Bioinformatics, biochemical and immunological methods were combined to elucidate the structure and function of SFTA3. The tissue-specific detection and characterisation was performed by using electron microscopy as well as fluorescence imaging. Three-dimensional structure generation and analysis led to the development of specific antibodies and, as a consequence, to the localisation of a novel protein in human lung under consideration of cystic fibrosis, asthma and sepsis. In vitro experiments revealed that lipopolysaccharide induces expression of SFTA3 in the human lung alveolar type II cell line A549. By contrast, the inflammatory cytokines interleukin (IL)-1β and IL-23 inhibit expression of SFTA3 in A549. Sequence- and structure-based prediction analysis indicated that the novel protein is likely to belong to the family of lung surfactant proteins. The results suggest that SFTA3 is an immunoregulatory protein of the lung with relevant protective functions during inflammation at the mucosal sites. SFTA3: a novel lung protein with putative protective and immunological functions during inflammation in lung diseases

Background Besides their prognostic impact blood pressure and peak heart rate are widely used endpoint parameters for incremental exercise tests. Reference equations and ranges on both are sparse. Objective This study aims to describe prediction equations and reference ranges for systolic and diastolic blood pressure as well as for peak heart rate assessed during a symptom limited incremental exercise test based on a population based study – the Study of Health in Pomerania. Design For this purpose, 1708 individuals aged 25–85 years underwent cardiopulmonary exercise testing. Results After exclusion of subjects with cardiopulmonary diseases and antihypertensive medications regression analyses revealed age, sex and body mass index as statistically significant interfering factors. In accordance, prediction equations and reference ranges for blood pressure and peak heart rate with respect to sex, age and BMI have been established. Conclusion This study provides a reliable set of prediction equations for blood pressure and heart rate values at peak exercise, assessed in a general population over a wide age range.

Background and objective: The assessment of static lung volumes and airway resistance is a frequently performed diagnostic procedure and considered as an important tool in medical surveillance to detect pulmonary diseases. The objectives of the study are to establish reference equations for body plethysmographic parameters in a representative adult population across a wide age range and to compare the normative values from this sample with previous ones. Methods: Body plethysmography was applied in 1809 participants (885 males) of a cross-sectional, population-based survey (Study of Health in Pomerania). Individuals with cardiopulmonary disorders and/or a pack-year smoking history >10 years and participants with a body mass index >30 kg/m2 were excluded. In total, 686 healthy individuals (275 males) aged 25–85 years were assessed. Results: Prediction equations for both genders were established by quantile regression analysis taking into account the influence of age, height and weight. Conclusions: The study provides a novel set of prediction equations for static lung volumes and airway resistance obtained using body plethysmography. Compared with our findings, existing equations underestimated some normal values. The results emphasize the need for up-to-date reference equations.

Pulmonary function measures reflect respiratory health and are used in the diagnosis of chronic obstructive pulmonary disease. We tested genome-wide association with forced expiratory volume in 1 second and the ratio of forced expiratory volume in 1 second to forced vital capacity in 48,201 individuals of European ancestry with follow up of the top associations in up to an additional 46,411 individuals. We identified new regions showing association (combined P < 5 x 10(-8)) with pulmonary function in or near MFAP2, TGFB2, HDAC4, RARB, MECOM (also known as EVI1), SPATA9, ARMC2, NCR3, ZKSCAN3, CDC123, C10orf11, LRP1, CCDC38, MMP15, CFDP1 and KCNE2. Identification of these 16 new loci may provide insight into the molecular mechanisms regulating pulmonary function and into molecular targets for future therapy to alleviate reduced lung function.

Objective There is cumulative evidence for a strong association of obstructive lung disease, i.e. asthma and COPD, with poor mental health, particularly with anxiety disorders and major depression. However, studies relating mental health problems to objective measures of lung function as assessed by spirometry are lacking. Methods The 12-month prevalence of specific psychopathological syndromes among 1772 adults from the general population was estimated by a structured interview. Additionally, participants underwent spirometry and were asked about obstructive lung disease in the year prior to the study. Logistic and linear regression models were used to relate obstructive lung disease and spirometrically defined airway obstruction to mental health problems. Results Mental health problems were found in 35.7% of the participants. After adjusted for sociodemographic, clinical and life-style factors, asthma and chronic bronchitis were associated with almost all domains of mental health problems. In contrast, independent of its definition, spirometric airflow limitation was only related to generalized anxiety (odds ratios ranging from 2.3 to 2.7). A reduced ratio of forced expiratory volume in one second to forced vital capacity was associated with mental health problems in general and panic and general anxiety in particular. Conclusion Our findings suggest an association of objective measure of airflow limitation to generalized anxiety and panic. While the causal relationship between obstructive lung disease, airflow limitation and anxiety remains to be determined, clinicians should pay diagnostic attention to the significant overlap of these conditions.

Studies on the relation between thyroid function and exercise blood pressure (EBP) are rare and not population-based, and have yielded inconsistent results. The aim of this study was to investigate whether serum thyrotropin (TSH) levels are related to increased EBP.Cross-sectional data from 1438 subjects (711 women) aged 25-83 years without histories of cardiovascular diseases from the 5-year follow-up of the population-based Study of Health in Pomerania (SHIP-1) were analyzed. Blood pressure was measured at the 100 W stage of a symptom-limited bicycle ergometry test. Increased EBP was defined as a value above the sex- and age-specific 80th percentile of participants with serum TSH levels within the reference range (0.25-2.12 mIU/L).There was no association between serum TSH levels and EBP after adjusting for sex, age, waist circumference, diabetes mellitus, smoking status, and antihypertensive medication. The odds for increased systolic EBP (odds ratio 1.24, 95% confidence interval 0.88; 1.76) and diastolic EBP (odds ratios 0.98, 95% confidence interval 0.70; 1.39) as well as for exercise-induced increase of systolic and diastolic blood pressure were not significantly different between subjects with high and low serum TSH levels within the reference range. Similar findings were found for both subjects with TSH levels below and above the reference range, respectively.We conclude that serum TSH levels are not associated with exercise-related blood pressure response.

Summary Background Spirometry is a frequently performed lung function test and an important tool in medical surveillance examinations of pulmonary diseases. The interpretation of lung function relies on the comparison to reference values derived from a healthy population. The study aim was to compare the lung function data of three representative population-based German studies (Study of Health in Pomerania [SHIP-1], Cooperative Health Research in the Region of Augsburg [KORA-S3] and European Community Respiratory Health Survey Erfurt [ECRHS-I Erfurt]) with existing European spirometry reference values and to establish a new set of comprehensive German prediction equations. Methods Spirometry was performed in 4133 participants of three population-based surveys using almost identical standardised methods. Current and former smokers, subjects with cardiopulmonary disorders or on medication with potential influence on lung function were excluded. Sex specific prediction equations were established by quantile regression analyses. Comparison was performed to existing European reference values. Results The healthy reference sample consisted of 1302 (516 male) individuals, aged 20–80 years. Sex specific comprehensive prediction equations adjusted for age and height are provided. Significant differences were found in comparison to previous studies with pronounced lower values of the current population if applying historic prediction equations. Conclusion The results contribute to the interpretation of lung function examination in providing a comprehensive set of spirometry reference values obtained in a large number of healthy volunteers. Whereas the differences in between the investigated studies are negligible, striking divergence was detected in comparison to historic and recent European spirometry prediction values.

Henry Volzke, y Dietrich Alte,1y Carsten Oliver Schmidt, Dorte Radke, Roberto Lorbeer, Nele Friedrich, Nicole Aumann, Katharina Lau, Michael Piontek, Gabriele Born, Christoph Havemann, Till Ittermann, Sabine Schipf, Robin Haring, Sebastian E Baumeister, Henri Wallaschofski, Matthias Nauck, Stephanie Frick, Andreas Arnold, Michael Junger, Julia Mayerle, Matthias Kraft, Markus M Lerch, Marcus Dorr, Thorsten Reffelmann, Klaus Empen, Stephan B Felix, Anne Obst, Beate Koch, Sven Glaser, Ralf Ewert, Ingo Fietze, Thomas Penzel, Martina Doren, Wolfgang Rathmann, Johannes Haerting, Mario Hannemann, Jurgen Ropcke, Ulf Schminke, Clemens Jurgens, Frank Tost, Rainer Rettig, Jan A Kors, Saskia Ungerer, Katrin Hegenscheid, Jens-Peter Kuhn, Julia Kuhn, Norbert Hosten, Ralf Puls, Jorg Henke, Oliver Gloger, Alexander Teumer, Georg Homuth, Uwe Volker, Christian Schwahn, Birte Holtfreter, Ines Polzer, Thomas Kohlmann, Hans J Grabe, Dieter Rosskopf, Heyo K Kroemer, Thomas Kocher, Reiner Biffar,17,y Ulrich John20y and Wolfgang Hoffmann1y

Background Insulin-like growth factor I (IGF-I) and its binding protein 3 (IGFBP-3) are central mediators of endocrine effects of growth hormone and there is increasing evidence for an association with muscle strength and exercise capacity. The aim of the present study was to clarify the possible association of circulating IGF-I and IGFBP-3 concentrations and exercise capacity in a general adult population. Materials and methods From the Study of Health in Pomerania (SHIP) 1332 subjects aged 25 to 85 years participated in a standardised symptom limited cardiopulmonary exercise test on a bicycle. Exercise capacity was characterized by oxygen uptake at anaerobic threshold (VO 2 @AT), peak exercise (peakVO 2 ), oxygen pulse and maximum power output at peak exertion. Multivariable linear regression analyses adjusted for age, sex, body mass index, physical activity and smoking were performed. Results At peak exercise performance, in women IGF-I showed significant associations to peakVO 2 and maximum power output, IGF-I/IGFBP-3 ratio was associated with maximum power output. In men, this association was not consistently reproducible. Neither IGF-I nor IGFBP-3 did reveal any association to VO 2 @AT in both genders. Conclusion Serum IGF-I concentrations are associated with peak exercise capacity in healthy women, but not in men over a wide range in ages, body sizes and activity scores.

Nachruf

Testosterone exerts a widespread pattern of effects on metabolism and body composition, and interest is gaining in its correlation with physical fitness. The main focus of our study was to investigate the association of total serum testosterone and sex hormone–binding globulin (SHBG) levels on exercise capacity and maximal power output in men using a cross-sectional, population-based adult cohort. From the Study of Health in Pomerania (SHIP), 624 men age 25 to 85 years who underwent a standardized progressive incremental exercise protocol on a cycle ergometer were included in the analyses. Exercise capacity was characterized by oxygen uptake at anaerobic threshold (V′O2 at θL) and peak exercise (V′O2peak) as well as maximal power output at peak exertion. Multivariable linear regression analyses adjusted for age, sex, body mass index, physical activity, and smoking were performed. Further, linear regression analyses with cubic splines and sensitivity analyses were undertaken. At peak exercise performance, testosterone and SHBG levels showed no associations with V′O2peak, V′O2 at θL as well as maximal power output, even after controlling for confounding factors including age, body mass index, physical activity, and smoking. An adverse association between the free testosterone index and V′O2 at θL was found. Linear regression analyses with cubic splines did not change the main results. In conclusion, this is the first study focusing on the association of total serum testosterone and SHBG on exercise capacity and physical performance in healthy volunteers based on a large-scale population-based study. After adjustment for relevant influencing factors, neither total serum testosterone nor SHBG levels had any interference with peak exercise capacity, aerobic exercise capacity, or maximal power output in men.

Background. Against the background of an increasing prevalence of allergies, the epidemiology of asthma in relation to age is still a matter of debate. To further clarify the prevalence of asthma, asthmatic symptoms, and their change over time within a population sample, we analyzed longitudinal data from the Study of Health in Pomerania (SHIP). Methods. Standardized questionnaires for asthma and asthmatic symptoms were available in 4310 individuals aged 20–75 years. The population sample underwent a 5-year follow-up with 3300 subjects reexamined. The questionnaire evaluated estimates to describe the prevalence in wheeze, chest tightness, shortness of breath, coughing, nocturnal symptoms, and asthma attacks in the past 12 months, current medications, current asthma, and nasal allergies at baseline and its longitudinal net change. Results. The prevalence of current asthma at the baseline study was 1.8% [95% confidence interval (CI 1.4–2.2)], those of nasal allergies 16.7% (95% CI 15.6–17.9). Sixteen percen...

Increased end-tidal oxygen (ET-O(2)) and decreased end-tidal carbon dioxide (ET-CO(2)) gas tensions are noninvasively measurable correlates of ventilatory inefficiency, leading to increased ventilatory requirements relative to gas exchange among patients with chronic heart failure (CHF). We investigated the prognostic value of ET-O(2) and ET-CO(2) as predictors of CHF mortality.We measured resting ET-O(2) and ET-CO(2) electrochemically in 134 patients with symptomatic CHF in the supine position. We used Kaplan-Meier analysis, Cox proportional hazard models, and receiver operating characteristic curves to test our hypothesis.At a median follow-up of 16.5 months, 32 patients had died. ET-O(2) levels were increased (P = .001) and ET-CO(2) levels decreased (P = .002) with increased New York Heart Association class (I-IV). Survivors showed lower ET-O(2) (121 vs 118 mm Hg; P = .021) and higher ET-CO(2) (33.2 vs 32.1 mm Hg; P = .032) levels than nonsurvivors. Patients with ET-O(2) values ≥121 mm Hg and/or ET-CO(2) values31 mm Hg had an increased risk of death with hazard ratios of 2.93 (95% confidence interval [CI], 1.43-6.01) and 2.47 (95% CI, 1.23-4.97), respectively. Kaplan-Meier estimates for follow-up mortality with ET-O(2) ≥121 mm Hg and/or ET-CO(2)31 mm Hg were 83.8% (vs 60.1%; P = .0014) and 80.3% (vs 60.2%; P = .0061), respectively. Areas under the receiver operating characteristic curves for prediction of death with ET-O(2) and ET-CO(2) were both significant and similar to that of echocardiographic left ventricular function.In CHF, high levels of ET-O(2) and low levels of ET-CO(2) are associated with increased mortality. We suggest that the measurements may be useful prognostic markers for risk stratification.

Trauma exposure and post-traumatic stress disorder (PTSD) are associated with self-reported asthma and chronic obstructive pulmonary disease. However, these conditions have not yet been related to objective measures of lung function. 1,772 adults from the general population were assessed regarding their medical histories and spirometric lung function. Additionally, they were administered a PTSD interview, and assigned to three groups: no trauma; trauma, but no PTSD; and trauma with PTSD. Adjusting for sociodemographic, clinical and lifestyle factors, subjects with PTSD had significantly higher odds ratios for most asthma-related symptoms than PTSD-negative participants (OR 3.2-8.8). The mean ratio of forced expiratory volume in 1 s (FEV₁) to forced vital capacity (FVC) was lowest in the PTSD group and highest in those without trauma exposure. Traumatic stress was independently associated with FEV₁ and FEV₁/FVC. Participants with PTSD, compared with those without, had a significantly increased risk for airflow limitation independent of its definition (OR 4.2-7.8). This is the first study relating traumatic stress and PTSD, respectively, to objective parameters of lung function. Our findings suggest an association of trauma exposure and PTSD with airflow limitation, which may be mediated by inflammatory processes.

Summary Background and Objective: Respiratory muscle pressures have been gaining increasing interest because of prognostic value. The study aim was to acquire reference values for respiratory pressures in a large-scale population-based survey – the Study of Health in Pomerania (SHIP). Methods: One thousand eight hundred and nine participants (885 men) of a cross-sectional epidemiologic survey, called ‘Study of Health in Pomerania – SHIP’, underwent lung function and respiratory muscle pressure measurements. After excluding individuals with cardiopulmonary disorders, prediction equations for men and women were established by quantile regression analysis. Results: The final study population comprised 912 individuals (432 men), aged 25–80 years. The study provides a representative set of sex-specific prediction equations of respiratory muscle strength. Respiratory pressures are decreasing with age and are lower in women when compared to men. Conclusions: Prediction equations for relevant respiratory pressures are given. Based on this well-described population-based survey with extensive cardiopulmonary investigations to exclude relevant interfering disorders a sufficient comprehensive set of reference values was obtained.

Das Wissen um die Ursachen und daraus abgeleitet die moglichen Behandlungsprinzipien des pathophy-siologischen Zustands einer Druckerhohung im kleinen Kreislauf (pulmonale Hypertonie, PH) ist in den vergangenen Jahrzehnten sprunghaft gestiegen. Diese Entwicklung findet ihren Niederschlag u. a. in den aktuellen Leitlinien zur Diagnostik und Therapie von Patienten mit PH. Mit dem vorliegenden Beitrag soll eine Ubersicht zu den wesentlichen Inhalten dieser Empfehlungen gegeben werden. Der Schwerpunkt liegt hierbei auf der Diagnostik und den medikamentosen Behandlungsmoglichkeiten einer ausgewahlten Gruppe von Patienten mit PH, namlich jenen mit einer pulmonalen arteriellen Hypertonie (PAH).

Background: Recent surveys report a surprisingly high prevalence of chronic obstructive pulmonary disease (COPD) worldwide. However, there is evidence that the application of a fixed ratio of forced expiratory volume in 1 s (FEV1) to forced vital capacity (FVC) may result in a relevant misclassification of airflow limitation. Objectives: The definition of airflow limitation does have a significant impact on its prevalence. Methods: Individual values of lung volumes were assessed in comparison to a reference population by applying either a fixed ratio below 0.7 or the fifth percentile of FEV1 in relation to FVC. Based on a large-scale population-based survey, reference equations for lung volumes were derived by quantile regression analysis based on 1,809 subjects aged 25–85 years. Both functional definitions were applied to calculate the prevalence of airflow limitation. Results: The prevalence of airflow limitation was significantly higher when applying the fifth percentile compared to the fixed ratio of 0.7 for all age groups and both sexes (all 6.7 vs. 1.9%; women 6.7 vs. 1.3%; men 6.6 vs. 2.6%). Almost 26% of the subjects with airflow limitation complained of dyspnea, whereas COPD had not been previously diagnosed by a physician in 87%. Conclusion: The definition of airflow limitation has a major impact on the observed prevalence rates.

Ein 37-jahriger Inder wurde mit persistierendem Husten und hohem Fieber stationar aufgenommen. Umfassende Untersuchungen sicherten die Diagnose einer Lungentuberkulose. Die kalkulierte antituberkulose Therapie erfolgte mit Pyrazinamid, Rifampicin, Ethambutol und Isoniazid. Obwohl die isolierten Erreger im Resistenztest sensibel waren, persistierten die Fieberschube. Eine Resorptionsstorung wurde immunhistochemisch ausgeschlossen. Erst im Verlauf trat unter der Standardbehandlung eine Stabilisierung ein; nach 10 Wochen bestand erstmalig kein Fieber mehr.

SummaryPulmonary hypertension is a relevant interceding morbidity in patients with pulmonary fibrosis that has significant impact on exercise tolerance and outcome. The aim of this study was to further characterize the exercise intolerance, dyspnoea and ventilatory inefficiency of patients with pulmonary fibrosis in the presence or absence of pulmonary hypertension via cardiopulmonary exercise testing.Thirty-four patients underwent pulmonary function testing, symptom-limited exercise testing on a bicycle and dyspnoea evaluation according to the BORG scale. Pulmonary hypertension was assessed by echocardiography and in a subset of patient's right heart catheterization.Sixteen of 34 patients with pulmonary fibrosis revealed pulmonary hypertension. While all study patients did not differ in lung functions and demographic characteristics, patients suffering from pulmonary hypertension showed a significantly impaired exercise tolerance and worsened ventilatory inefficiency. The extent of pulmonary artery pressure elevation impacted significantly on ventilatory inefficiency. In addition, the increased ventilatory requirements significantly influenced the extent of dyspnoea in patients with pulmonary hypertension.We conclude that pulmonary hypertension has a significant impact on exercise capacity and dyspnoea in patients with interstitial lung disease (ILD). The further impairment of exercise capacity as well as the extent of dyspnoea in patients with interceding PHT is attributable to a significantly impaired ventilatory inefficiency.

In recent years, skeletal age determination has become increasingly important for determining the age of live subjects as part of criminal investigation. The most widely used method worldwide to determine skeletal age is the Greulich-Pyle atlas method. The present study examines the suitability of the Greulich-Pyle method given the particular requirements of forensic age estimates. It is a retrospective analysis of 649 hand radiographs originally taken from persons aged between 1 and 18 years, separately for each sex. If the Greulich-Pyle method is used exclusively, it can be claimed with a probability of 95% that a young man has reached the age of 14 years and thus the age of criminal liability if his skeletal age is at least 15.5 years. In the case of female subjects, even if they are estimated as being 16.0 years old, it cannot be asserted with a probability of 95% that they have reached the age of 14. To reduce the margin of error of age estimates, determining the skeletal age should always go hand in hand with a physical examination to determine indications of sexual maturity and a dental examination to record dental status. The reference values given in the present study can be applied to members of all ethnic groups for age estimate purposes. If the person under examination has a different socio-economic status, the expert performing the age estimate should address this issue in his expert opinion and discuss the possible effects that might have on the age diagnosis.

Die Mobile-Marketing-Masnahmen sollten an den Konsumentenbedurfnissen entlang des Kaufentscheidungsprozesses orientiert werden. Interessant fur Werbetreibende ist daher die Frage, welche Relevanz mobile Endgerate im Kaufentscheidungsprozess haben und wozu sie eingesetzt werden. Dieser Beitrag zielt daher darauf ab zu untersuchen, ob es fur Konsumguterhersteller sinnvoll ist, ihre Mobile-Marketing-Aktivitaten an den Konsumentenbedurfnissen entlang des Kaufentscheidungsprozesses auszurichten. Zudem sollen Empfehlungen abgegeben werden, welche Mobile-Marketing-Instrumente in den einzelnen Phasen geeignet sind, um die jeweiligen Konsumentenbedurfnisse zu befriedigen bzw. relevante Botschaften zu senden.

BACKGROUND: Genome-wide association studies (GWAS) have identified numerous loci influencing cross-sectional lung function, but less is known about genes influencing longitudinal change in lung function.METHODS: We performed GWAS of the rate of change in forced expiratory volume in the first second (FEV1) in 14 longitudinal, population-based cohort studies comprising 27,249 adults of European ancestry using linear mixed effects model and combined cohort-specific results using fixed effect meta-analysis to identify novel genetic loci associated with longitudinal change in lung function. Gene expression analyses were subsequently performed for identified genetic loci. As a secondary aim, we estimated the mean rate of decline in FEV1 by smoking pattern, irrespective of genotypes, across these 14 studies using meta-analysis.RESULTS: The overall meta-analysis produced suggestive evidence for association at the novel IL16/STARD5/TMC3 locus on chromosome 15 (P = 5.71 × 10-7). In addition, meta-analysis using the five cohorts with ≥3 FEV1 measurements per participant identified the novel ME3 locus on chromosome 11 (P = 2.18 × 10-8) at genome-wide significance. Neither locus was associated with FEV1 decline in two additional cohort studies. We confirmed gene expression of IL16, STARD5, and ME3 in multiple lung tissues. Publicly available microarray data confirmed differential expression of all three genes in lung samples from COPD patients compared with controls. Irrespective of genotypes, the combined estimate for FEV1 decline was 26.9, 29.2 and 35.7 mL/year in never, former, and persistent smokers, respectively.CONCLUSIONS: In this large-scale GWAS, we identified two novel genetic loci in association with the rate of change in FEV1 that harbor candidate genes with biologically plausible functional links to lung function.

Several infrequent genetic polymorphisms in the SERPINA1 gene are known to substantially reduce concentration of alpha1-antitrypsin (AAT) in the blood. Since low AAT serum levels fail to protect pulmonary tissue from enzymatic degradation, these polymorphisms also increase the risk for early onset chronic obstructive pulmonary disease (COPD). The role of more common SERPINA1 single nucleotide polymorphisms (SNPs) in respiratory health remains poorly understood. We present here an agnostic investigation of genetic determinants of circulating AAT levels in a general population sample by performing a genome-wide association study (GWAS) in 1392 individuals of the SAPALDIA cohort. Five common SNPs, defined by showing minor allele frequencies (MAFs) >5%, reached genome-wide significance, all located in the SERPINA gene cluster at 14q32.13. The top-ranking genotyped SNP rs4905179 was associated with an estimated effect of β = −0.068 g/L per minor allele (P = 1.20*10−12). But denser SERPINA1 locus genotyping in 5569 participants with subsequent stepwise conditional analysis, as well as exon-sequencing in a subsample (N = 410), suggested that AAT serum level is causally determined at this locus by rare (MAF, Author Summary Low levels of alpha1-antitrypsin (AAT) in the blood are a well-established risk factor for accelerated loss in lung function and chronic obstructive pulmonary disease. While a few infrequent genetic polymorphisms are known to influence the serum levels of this enzyme, the role of common genetic variants has not been examined so far. The present genome-wide scan for associated variants in approximately 1400 Swiss inhabitants revealed a chromosomal locus containing the functionally established variants of AAT deficiency and variants previously associated with lung function and emphysema. We used dense genotyping of this genetic region in more than 5500 individuals and subsequent conditional analyses to unravel which of these associated variants contribute independently to the phenotype's variability. All associations of common variants could be attributed to the rarer functionally established variants, a result which was then replicated in an independent population-based Danish cohort. Hence, this locus represents a textbook example of how a large part of a trait's heritability can be hidden in infrequent genetic polymorphisms. The attempt to transfer these results to lung function furthermore suggests that effects of common variants in this genetic region in ever-smokers may also be explained by rarer variants, but only in individuals with hampered pulmonary health.

The assessment of static lung volumes and airway resistance is a frequently performed diagnostic procedure and considered as an important tool in medical surveillance to detect pulmonary diseases. The objectives of the study are to establish reference equations for body plethysmographic parameters in a representative adult population across a wide age range and to compare the normative values from this sample with previous ones.Body plethysmography was applied in 1809 participants (885 males) of a cross-sectional, population-based survey (Study of Health in Pomerania). Individuals with cardiopulmonary disorders and/or a pack-year smoking history10 years and participants with a body mass index30 kg/m(2) were excluded. In total, 686 healthy individuals (275 males) aged 25-85 years were assessed.Prediction equations for both genders were established by quantile regression analysis taking into account the influence of age, height and weight.The study provides a novel set of prediction equations for static lung volumes and airway resistance obtained using body plethysmography. Compared with our findings, existing equations underestimated some normal values. The results emphasize the need for up-to-date reference equations.

Genome-wide association studies have identified numerous genetic loci for spirometic measures of pulmonary function, forced expiratory volume in one second (FEV1), and its ratio to forced vital capacity (FEV1/FVC). Given that cigarette smoking adversely affects pulmonary function, we conducted genome-wide joint meta-analyses (JMA) of single nucleotide polymorphism (SNP) and SNP-by-smoking (ever-smoking or pack-years) associations on FEV1 and FEV1/FVC across 19 studies (total N = 50,047). We identified three novel loci not previously associated with pulmonary function. SNPs in or near DNER (smallest P JMA = 5.00×10−11), HLA-DQB1 and HLA-DQA2 (smallest P JMA = 4.35×10−9), and KCNJ2 and SOX9 (smallest P JMA = 1.28×10−8) were associated with FEV1/FVC or FEV1 in meta-analysis models including SNP main effects, smoking main effects, and SNP-by-smoking (ever-smoking or pack-years) interaction. The HLA region has been widely implicated for autoimmune and lung phenotypes, unlike the other novel loci, which have not been widely implicated. We evaluated DNER, KCNJ2, and SOX9 and found them to be expressed in human lung tissue. DNER and SOX9 further showed evidence of differential expression in human airway epithelium in smokers compared to non-smokers. Our findings demonstrated that joint testing of SNP and SNP-by-environment interaction identified novel loci associated with complex traits that are missed when considering only the genetic main effects., Author Summary Measures of pulmonary function provide important clinical tools for evaluating lung disease and its progression. Genome-wide association studies have identified numerous genetic risk factors for pulmonary function but have not considered interaction with cigarette smoking, which has consistently been shown to adversely impact pulmonary function. In over 50,000 study participants of European descent, we applied a recently developed joint meta-analysis method to simultaneously test associations of gene and gene-by-smoking interactions in relation to two major clinical measures of pulmonary function. Using this joint method to incorporate genetic main effects plus gene-by-smoking interaction, we identified three novel gene regions not previously related to pulmonary function: (1) DNER, (2) HLA-DQB1 and HLA-DQA2, and (3) KCNJ2 and SOX9. Expression analyses in human lung tissue from ours or prior studies indicate that these regions contain genes that are plausibly involved in pulmonary function. This work highlights the utility of employing novel methods for incorporating environmental interaction in genome-wide association studies to identify novel genetic regions.

Lung function measures are heritable traits that predict population morbidity and mortality and are essential for the diagnosis of chronic obstructive pulmonary disease (COPD). Variations in many genes have been reported to affect these traits, but attempts at replication have provided conflicting results. Recently, we undertook a meta-analysis of Genome Wide Association Study (GWAS) results for lung function measures in 20,288 individuals from the general population (the SpiroMeta consortium). OBJECTIVES: To comprehensively analyse previously reported genetic associations with lung function measures, and to investigate whether single nucleotide polymorphisms (SNPs) in these genomic regions are associated with lung function in a large population sample. METHODS: We analysed association for SNPs tagging 130 genes and 48 intergenic regions (+/-10 kb), after conducting a systematic review of the literature in the PubMed database for genetic association studies reporting lung function associations. The analysis included 16,936 genotyped and imputed SNPs. No loci showed overall significant association for FEV(1) or FEV(1)/FVC traits using a carefully defined significance threshold of 1.3×10(-5). The most significant loci associated with FEV(1) include SNPs tagging MACROD2 (P = 6.81×10(-5)), CNTN5 (P = 4.37×10(-4)), and TRPV4 (P = 1.58×10(-3)). Among ever-smokers, SERPINA1 showed the most significant association with FEV(1) (P = 8.41×10(-5)), followed by PDE4D (P = 1.22×10(-4)). The strongest association with FEV(1)/FVC ratio was observed with ABCC1 (P = 4.38×10(-4)), and ESR1 (P = 5.42×10(-4)) among ever-smokers.CONCLUSIONS: Polymorphisms spanning previously associated lung function genes did not show strong evidence for association with lung function measures in the SpiroMeta consortium population. Common SERPINA1 polymorphisms may affect FEV(1) among smokers in the general population.

Against the background of an increasing prevalence of allergies, the epidemiology of asthma in relation to age is still a matter of debate. To further clarify the prevalence of asthma, asthmatic symptoms, and their change over time within a population sample, we analyzed longitudinal data from the Study of Health in Pomerania (SHIP).Standardized questionnaires for asthma and asthmatic symptoms were available in 4310 individuals aged 20–79 years [corrected]. The population sample underwent a 5-year follow-up with 3300 subjects reexamined. The questionnaire evaluated estimates to describe the prevalence in wheeze, chest tightness, shortness of breath, coughing, nocturnal symptoms, and asthma attacks in the past 12 months, current medications, current asthma, and nasal allergies at baseline and its longitudinal net change.The prevalence of current asthma at the baseline study was 1.8% [95% confidence interval (CI 1.4–2.2)], those of nasal allergies 16.7% (95% CI 15.6–17.9). Sixteen percent of asthmatic individuals were not medically treated. The net changes in asthmatic symptoms per 60 months of follow-up ranged between a decrease by 2.0% (chest tightness at night) and an increase by 1.2% (nocturnal attack of coughing). The proportions of subjects with current asthma remained unchanged. The prevalence of current asthma and symptoms was higher in young individuals, whereas the net change over time was slightly increasing at the age of 36 and above.Despite the fact of a high prevalence of subjects complaining of nasal allergies, the overall prevalence of current asthma remained low over time. The prevalence in asthma and asthmatic symptoms as well as its net changes over 5 years were age dependent.

Respiratory muscle pressures have been gaining increasing interest because of prognostic value. The study aim was to acquire reference values for respiratory pressures in a large-scale population-based survey--the Study of Health in Pomerania (SHIP).One thousand eight hundred and nine participants (885 men) of a cross-sectional epidemiologic survey, called 'Study of Health in Pomerania--SHIP', underwent lung function and respiratory muscle pressure measurements. After excluding individuals with cardiopulmonary disorders, prediction equations for men and women were established by quantile regression analysis.The final study population comprised 912 individuals (432 men), aged 25-80 years. The study provides a representative set of sex-specific prediction equations of respiratory muscle strength. Respiratory pressures are decreasing with age and are lower in women when compared to men.Prediction equations for relevant respiratory pressures are given. Based on this well-described population-based survey with extensive cardiopulmonary investigations to exclude relevant interfering disorders a sufficient comprehensive set of reference values was obtained.

SummaryBackgroundIn patients with moderate to severe allergic asthma, clinical effectiveness of omalizumab, an approved anti-IgE-reacting substance, is usually assessed by pulmonary function testing (PFT), symptom scores and physicians judgement.AimsWe postulate that cardiopulmonary exercise testing (CPET) may provide an additional option to verify symptomatic changes in patients with allergic asthma.MethodsTen consecutive patients with allergic asthma were treated with omalizumab. Prior to and after 16 weeks of treatment all patients underwent PFT and symptom-limited CPET. Results were compared to 10 asthmatic controls without omalizumab medication. Symptoms were assessed according to investigators judgement (IGETE).ResultsAll 20 patients showed a significantly impaired exercise capacity at baseline [peak oxygen uptake (VO2) 71 ± 16% predicted]. In patients with omalizumab, peakVO2 increased from 13.8 (8.4–21.4) to 16.8 (11.2–23.9) ml/kg/min (p

Background Little is known about the influencing potential of specific characteristics on lung function in different populations. The aim of this analysis was to determine whether lung function determinants differ between subpopulations within Germany and whether prediction equations developed for one subpopulation are also adequate for another subpopulation. Methods Within three studies (KORA C, SHIP-I, ECRHS-I) in different areas of Germany 4059 adults performed lung function tests. The available data consisted of forced expiratory volume in one second, forced vital capacity and peak expiratory flow rate. For each study multivariate regression models were developed to predict lung function and Bland-Altman plots were established to evaluate the agreement between predicted and measured values. Results The final regression equations for FEV1 and FVC showed adjusted r-square values between 0.65 and 0.75, and for PEF they were between 0.46 and 0.61. In all studies gender, age, height and pack-years were significant determinants, each with a similar effect size. Regarding other predictors there were some, although not statistically significant, differences between the studies. Bland-Altman plots indicated that the regression models for each individual study adequately predict medium (i.e. normal) but not extremely high or low lung function values in the whole study population. Conclusions Simple models with gender, age and height explain a substantial part of lung function variance whereas further determinants add less than 5% to the total explained r-squared, at least for FEV1 and FVC. Thus, for different adult subpopulations of Germany one simple model for each lung function measures is still sufficient.

Cardiopulmonary exercise testing (CPET) is a widely applied clinical procedure. There is uncertainty to what extent nutritional status, beta blockers and smoking should be taken into account in the interpretation of exercise parameters to describe abnormality. This study planned to consider the impact of these factors on CPET values and develop reference equations on the basis of a large-scale population-based survey.An incremental cycle exercise protocol was applied to 1708 volunteers. Individuals with structural heart disease, echocardiographic or lung function pathologies were excluded. Age, height, weight, smoking, and beta blockers were analysed for their influencing power in each sex. Reference values of CPET parameters were determined by regression analyses. The final study sample consisted of 1203 volunteers (626 female), aged 25-85 years. Exercise capacity, gas exchange, and ventilatory efficiency for carbon dioxide removal were significantly dependent on sex, age, height, weight, and cigarette smoking. In the dosages used, beta blockers did not significantly interfere with gas exchange.Sex, height, weight, and age significantly influence gas exchange. This study provides a comprehensive set of reference values in a large number of volunteers within a population-based survey, with reference values corrected for influencing factors.