ERS technical standard: Global Lung Function Initiative reference values for exhaled nitric oxide fraction (F ENO50 ).

BACKGROUND: Elevated exhaled nitric oxide fraction at a flow rate of 50 mL·s-1 (F ENO50 ) is an important indicator of T-helper 2-driven airway inflammation and may aid clinicians in the diagnosis and monitoring of asthma. This study aimed to derive Global Lung Function Initiative reference equations and the upper limit of normal for F ENO50 . METHODS: Available individual F ENO50 data were collated and harmonised using consensus-derived variables and definitions. Data collected from individuals who met the harmonised definition of "healthy" were analysed using the generalised additive models of location, scale and shape (GAMLSS) technique. RESULTS: Data were retrospectively collated from 34 782 individuals from 34 sites in 15 countries, of whom 8022 met the definition of healthy (19 sites, 11 countries). Overall, height, age and sex only explained 12% of the between-subject variability of F ENO50 (R2=0.12). F ENO device was neccessary as a predictor of F ENO50 , such that the healthy range of values and the upper limit of normal varied depending on which device was used. The range of F ENO50 values observed in healthy individuals was also very wide, and the heterogeneity was partially explained by the device used. When analysing a subset of data in which F ENO50 was measured using the same device and a stricter definition of health (n=1027), between-site heterogeneity remained. CONCLUSION: Available F ENO50 data collected from different sites using different protocols and devices were too variable to develop a single all-age reference equation. Further standardisation of F ENO devices and measurement are required before population reference values might be derived.

[Workplace-associated fever]. / Arbeitsplatzassoziiertes Fieber oder wenn es doch das Zebra ist .

INTRODUCTION: Febrile conditions often have an infectious etiology. However, there are also fevers associated with occupational exposures. A detailed occupational history can hold the key to the diagnosis. In the case of exposure to organic dusts, the development of hypersensitivity pneumonitis (HP) is possible. Thus, HP should be considered in the presence of interstitial lung disease of unclear etiology. Failure to recognize this can have dramatic consequences and, in extreme cases, lead to lung transplantation. Differentially, organic dust toxic syndrome (ODTS) must be considered. The syndrome of metal fume fever provoked by inhalation of inorganic substances is usually benign and self-limiting. The disease manifests with fever, cough, and flu-like sensations.

Frequency-based rare diagnoses as a novel and accessible approach for studying rare diseases in large datasets: a cross-sectional study.

BACKGROUND: Up to 8% of the general population have a rare disease, however, for lack of ICD-10 codes for many rare diseases, this population cannot be generically identified in large medical datasets. We aimed to explore frequency-based rare diagnoses (FB-RDx) as a novel method exploring rare diseases by comparing characteristics and outcomes of inpatient populations with FB-RDx to those with rare diseases based on a previously published reference list. METHODS: Retrospective, cross-sectional, nationwide, multicenter study including 830,114 adult inpatients. We used the national inpatient cohort dataset of the year 2018 provided by the Swiss Federal Statistical Office, which routinely collects data from all inpatients treated in any Swiss hospital. Exposure: FB-RDx, according to 10% of inpatients with the least frequent diagnoses (i.e.1.decile) vs. those with more frequent diagnoses (deciles 2-10). Results were compared to patients having 1 of 628 ICD-10 coded rare diseases. PRIMARY OUTCOME: In-hospital death. SECONDARY OUTCOMES: 30-day readmission, admission to intensive care unit (ICU), length of stay, and ICU length of stay. Multivariable regression analyzed associations of FB-RDx and rare diseases with these outcomes. RESULTS: 464,968 (56%) of patients were female, median age was 59 years (IQR: 40-74). Compared with patients in deciles 2-10, patients in the 1. were at increased risk of in-hospital death (OR 1.44; 95% CI: 1.38, 1.50), 30-day readmission (OR 1.29; 95% CI 1.25, 1.34), ICU admission (OR 1.50; 95% CI 1.46, 1.54), increased length of stay (Exp(B) 1.03; 95% CI 1.03, 1.04) and ICU length of stay (1.15; 95% CI 1.12, 1.18). ICD-10 based rare diseases groups showed similar results: in-hospital death (OR 1.82; 95% CI 1.75, 1.89), 30-day readmission (OR 1.37; 95% CI 1.32, 1.42), ICU admission (OR 1.40; 95% CI 1.36, 1.44) and increased length of stay (OR 1.07; 95% CI 1.07, 1.08) and ICU length of stay (OR 1.19; 95% CI 1.16, 1.22). CONCLUSION(S): This study suggests that FB-RDx may not only act as a surrogate for rare diseases but may also help to identify patients with rare disease more comprehensively. FB-RDx associate with in-hospital death, 30-day readmission, intensive care unit admission, and increased length of stay and intensive care unit length of stay, as has been reported for rare diseases.

A Multi-component Intervention (NEXpro) Reduces Neck Pain-Related Work Productivity Loss: A Randomized Controlled Trial Among Swiss Office Workers.

Purpose Neck pain is common among office workers and leads to work productivity loss. This study aimed to investigate the effect of a multi-component intervention on neck pain-related work productivity loss among Swiss office workers. Methods Office workers, aged 18-65 years, and without serious neck-related health problems were recruited from two organisations for our stepped-wedge cluster randomized controlled trial. The 12-week multi-component intervention included neck exercises, health-promotion information, and workplace ergonomics. The primary outcome of neck pain-related work productivity loss was measured using the Work Productivity and Activity Impairment Questionnaire and expressed as percentages of working time. In addition, we reported the weekly monetary value of neck pain-related work productivity loss. Data was analysed on an intention-to-treat basis using a generalized linear mixed-effects model. Results Data from 120 participants were analysed with 517 observations. At baseline, the mean age was 43.7 years (SD 9.8 years), 71.7% of participants were female (N = 86), about 80% (N = 95) reported mild to moderate neck pain, and neck pain-related work productivity loss was 12% of working time (absenteeism: 1.2%, presenteeism: 10.8%). We found an effect of our multi-component intervention on neck pain-related work productivity loss, with a marginal predicted mean reduction of 2.8 percentage points (b = -0.27; 95% CI: -0.54 to -0.001, p = 0.049). Weekly saved costs were Swiss Francs 27.40 per participant. Conclusions: Our study provides evidence for the effectiveness of a multi-component intervention to reduce neck pain-related work productivity loss with implications for employers, employees, and policy makers.Trial Registration ClinicalTrials.gov, NCT04169646. Registered 15 November 2019-Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT04169646 .

Humidification of indoor air for preventing or reducing dryness symptoms or upper respiratory infections in educational settings and at the workplace.

BACKGROUND: Indoor exposure to dry air during heating periods has been associated with dryness and irritation symptoms of the upper respiratory airways and the skin. The irritated or damaged mucous membrane poses an important entry port for pathogens causing respiratory infections. OBJECTIVES: To determine the effectiveness of interventions that increase indoor air humidity in order to reduce or prevent dryness symptoms of the eyes, the skin and the upper respiratory tract (URT) or URT infections, at work and in educational settings. SEARCH METHODS: The last search for all databases was done in December 2020. We searched Ovid MEDLINE, Embase, CENTRAL (Cochrane Library), PsycINFO, Web of Science, Scopus and in the field of occupational safety and health: NIOSHTIC-2, HSELINE, CISDOC and the In-house database of the Division of Occupational and Environmental Medicine, University of Zurich. We also contacted experts, screened reference lists of included trials, relevant reviews and consulted the WHO International Clinical Trials Registry Platform (ICTRP). SELECTION CRITERIA: We included controlled studies with a parallel group or cross-over design, quasi-randomised studies, controlled before-and-after and interrupted time-series studies on the effects of indoor air humidification in reducing or preventing dryness symptoms and upper respiratory tract infections as primary outcomes at workplace and in the educational setting. As secondary outcomes we considered perceived air quality, other adverse events, sick leave, task performance, productivity and attendance and costs of the intervention. DATA COLLECTION AND ANALYSIS: Two review authors independently screened titles, abstracts and full texts for eligibility, extracted data and assessed the risks of bias of included studies. We synthesised the evidence for the primary outcomes 'dry eye', 'dry nose', 'dry skin', for the secondary outcome 'absenteeism', as well as for 'perception of stuffiness' as the harm-related measure. We assessed the certainty of evidence using the GRADE system. MAIN RESULTS: We included 13 studies with at least 4551 participants, and extracted the data of 12 studies with at least 4447 participants. Seven studies targeted the occupational setting, with three studies comprising office workers and four hospital staff. Three of them were clustered cross-over studies with 846 participants (one cRCT), one parallel-group controlled trial (2395 participants) and three controlled before-and-after studies with 181 participants. Five studies, all CTs, with at least 1025 participants, addressing the educational setting, were reported between 1963 and 1975, and in 2018. In total, at least 3933 (88%) participants were included in the data analyses. Due to the lack of information, the results of the risk of bias assessment remained mainly unclear and the assessable risks of bias of included studies were considered as predominantly high. Primary outcomes in occupational setting:  We found that indoor air humidification at the workplace may have little to no effect on dryness symptoms of the eye and nose (URT). The only cRCT showed a significant decrease in dry eye symptoms among working adults (odds ratio (OR) 0.54, 95% confidence interval (CI) 0.37 to 0.79) with a low certainty of the evidence. The only cluster non-randomised cross-over study showed a non-significant positive effect of humidification on dryness nose symptoms (OR 0.87, 95% CI 0.53 to 1.42) with a low certainty of evidence. We found that indoor air humidification at the workplace may have little and non-significant effect on dryness skin symptoms. The pooled results of two cluster non-RCTs showed a non-significant alleviation of skin dryness following indoor air humidification (OR 0.66, 95% CI 0.33 to 1.32) with a low certainty of evidence. Similarly, the pooled results of two before-after studies yielded no statistically significant result (OR 0.69, 95% CI 0.33 to 1.47) with very low certainty of evidence No studies reported on the outcome of upper respiratory tract infections. No studies conducted in educational settings investigated our primary outcomes. Secondary outcomes in occupational setting: Perceived stuffiness of the air was increased during the humidification in the two cross-over studies (OR 2.18, 95% CI 1.47 to 3.23); (OR 1.70, 95% CI 1.10 to 2.61) with low certainty of evidence. Secondary outcomes in educational setting: Based on different measures and settings of absenteeism, four of the six controlled studies found a reduction in absenteeism following indoor air humidification (OR 0.54, 95% CI 0.45 to 0.65; OR 0.38, 95% CI 0.15 to 0.96; proportion 4.63% versus 5.08%). AUTHORS' CONCLUSIONS: Indoor air humidification at the workplace may have little to no effect on dryness symptoms of the eyes, the skin and the URT. Studies investigating illness-related absenteeism from work or school could only be summarised narratively, due to different outcome measures assessed. The evidence suggests that increasing humidification may reduce the absenteeism, but the evidence is very uncertain. Future RCTs involving larger sample sizes, assessing dryness symptoms more technically or rigorously defining absenteeism and controlling for potential confounders are therefore needed to determine whether increasing indoor air humidity can reduce or prevent dryness symptoms of the eyes, the skin, the URT or URT infections at work and in educational settings over time.

Discrepancies of asbestos body and fiber content between formalin-fixed and corresponding paraffin embedded lung tissue.

BACKGROUND: Formalin-fixed lung tissue and paraffin blocks containing peripheral lung tissue obtained from subjects with an occupational asbestos exposure are both regarded to be suitable to determine asbestos load. Because sample preparation of paraffin blocks requires a more intense treatment than formalin-fixed tissue, we tested whether asbestos analysis of formalin-fixed lung tissue and paraffin blocks obtained from the same patients deliver comparable results. MATERIALS AND METHODS: We determined numbers of asbestos bodies (AB) and amphibole asbestos fibers (AF) in formalin-fixed lung tissue and corresponding paraffin blocks from 36 patients. For AB counts, samples were digested in sodium hypochlorite. For AF analysis, tissue was freeze-dried and then ashed. Results were reported as numbers of AB and AF per gram dry lung tissue. RESULTS: Both AB counts as well as AF counts were lower in paraffin blocks than formalin-fixed lung tissue. Compared to formalin-fixed tissue, the limit of detection was higher for paraffin blocks, rendering more results from paraffin blocks not interpretable than from formalin-fixed tissue (8 samples versus 1 for AB and 15 samples versus 4 for AF). DISCUSSION AND CONCLUSION: Asbestos analysis of paraffin blocks may lead to underestimation of asbestos exposure. This should be considered when assessing occupational asbestos exposure through lung dust analysis in medico-legal evaluation.

Temporal trends and regional disparities in cancer screening utilization: an observational Swiss claims-based study.

BACKGROUND: We examined colorectal, breast, and prostate cancer screening utilization in eligible populations within three data cross-sections, and identified factors potentially modifying cancer screening utilization in Swiss adults. METHODS: The study is based on health insurance claims data of the Helsana Group. The Helsana Group is one of the largest health insurers in Switzerland, insuring approximately 15% of the entire Swiss population across all regions and age groups. We assessed proportions of the eligible populations receiving colonoscopy/fecal occult blood testing (FOBT), mammography, or prostate-specific antigen (PSA) testing in the years 2014, 2016, and 2018, and calculated average marginal effects of individual, temporal, regional, insurance-, supply-, and system-related variables on testing utilization using logistic regression. RESULTS: Overall, 8.3% of the eligible population received colonoscopy/FOBT in 2014, 8.9% in 2016, and 9.2% in 2018. In these years, 20.9, 21.2, and 20.4% of the eligible female population received mammography, and 30.5, 31.1, and 31.8% of the eligible male population had PSA testing. Adjusted testing utilization varied little between 2014 and 2018; there was an increasing trend of 0.8% (0.6-1.0%) for colonoscopy/FOBT and of 0.5% (0.2-0.8%) for PSA testing, while mammography use decreased by 1.5% (1.2-1.7%). Generally, testing utilization was higher in French-speaking and Italian-speaking compared to German-speaking region for all screening types. Cantonal programs for breast cancer screening were associated with an increase of 7.1% in mammography utilization. In contrast, a high density of relevant specialist physicians showed null or even negative associations with screening utilization. CONCLUSIONS: Variation in cancer screening utilization was modest over time, but considerable between regions. Regional variation was highest for mammography use where recommendations are debated most controversially, and the implementation of programs differed the most.

No evidence for an effect of working from home on neck pain and neck disability among Swiss office workers: Short-term impact of COVID-19.

PURPOSE: The aim of this study was to investigate the effect of working from home on neck pain (NP) among office workers during the COVID-19 pandemic. METHODS: Participants from two Swiss organisations, aged 18-65 years and working from home during the lockdown (n = 69) were included. Baseline data collected in January 2020 before the lockdown (office work) were compared with follow-up data in April 2020 during lockdown (working from home). The primary outcome of NP was assessed with a measure of intensity and disability. Secondary outcomes were quality of workstation ergonomics, number of work breaks, and time spent working at the computer. Two linear mixed effects models were fitted to the data to estimate the change in NP. RESULTS: No clinically relevant change in the average NP intensity and neck disability was found between measurement time points. Each working hour at the computer increased NP intensity by 0.36 points (95% CI: 0.09 to 0.62) indicating strong evidence. No such effect was found for neck disability. Each work break taken reduced neck disability by 2.30 points (95% CI: - 4.18 to - 0.42, evidence). No such effect was found for NP intensity. There is very strong evidence that workstation ergonomics was poorer at home. CONCLUSION: The number of work breaks and hours spent at the computer seem to have a greater effect on NP than the place of work (office, at home), measurement time point (before COVID-19, during lockdown) or the workstation ergonomics. Further research should investigate the effect of social and psychological factors. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04169646. Registered 15 November 2019-Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT04169646 .

How do patients enter the healthcare system after the first onset of multiple sclerosis symptoms? The influence of setting and physician specialty on speed of diagnosis.

BACKGROUND: Diagnosing multiple sclerosis (MS) early is crucial to avoid future disability. However, potentially preventable delays in the diagnostic cascade from contact with a physician to definite diagnosis still occur and their causes are still unclear. OBJECTIVE: To identify the possible causes of delays in the diagnostic process. METHODS: We analyzed the data of the Swiss MS Registry. With logistic regression, we modeled the time from the first contact to the first consultation (contact-to-evaluation time, ⩽1 month/>1 month) and the evaluation-to-diagnosis time (⩽6 months/>6 months). Potential factors were health system characteristics, sociodemographic variables, first symptoms, and MS type. RESULTS: We included 522 participants. Mostly, general practitioners (67%) were contacted first, without delaying the diagnosis. In contrast, first symptoms and MS type were the major contributors to delays: gait problems were associated with longer contact-to-evaluation times, depression as a concomitant symptom with longer evaluation-to-diagnosis times, and having primary progressive MS prolonged both phases. In addition, living in mountainous areas was associated with longer contact-to-evaluation times, whereas diagnosis after 2000 was associated with faster diagnoses. CONCLUSION: For a quicker diagnosis, awareness of MS as a differential diagnosis of gait disorders and the co-occurrence of depression at onset should be raised, and these symptoms should be attentively followed.

Going beyond the mean: economic benefits of myocardial infarction secondary prevention.

BACKGROUND: Using the example of secondary prophylaxis of myocardial infarction (MI), our aim was to establish a framework for assessing cost consequences of compliance with clinical guidelines; thereby taking cost trajectories and cost distributions into account. METHODS: Swiss mandatory health insurance claims from 1840 persons with hospitalization for MI in 2014 were analysed. Included persons were predominantly male (74%), had a median age of 73 years, and 71% were pre-exposed to drugs for secondary prophylaxis, prior to index hospitalization. Guideline compliance was defined as being prescribed recommended 4-class drug prophylaxis including drugs from the following four classes: beta-blockers, statins, aspirin or P2Y12 inhibitors, and angiotension-converting enzyme inhibitors or angiotensin receptor blockers. Health care expenditures (HCE) accrued over 1 year after index hospitalization were compared by compliance status using two-part regression, trajectory analysis, and counterfactual decomposition analysis. RESULTS: Only 32% of persons received recommended 4-class prophylaxis. Compliant persons had lower HCE (- 4865 Swiss Francs [95% confidence interval - 8027; - 1703]) and were more likely to belong to the most favorable HCE trajectory (with 6245 Swiss Francs average annual HCE and comprising 78% of all studied persons). Distributional analyses showed that compliance-associated HCE reductions were more pronounced among persons with HCE above the median. CONCLUSIONS: Compliance with recommended prophylaxis was robustly associated with lower HCE and more favorable cost trajectories, but mainly among persons with high health care expenditures. The analysis framework is easily transferrable to other diseases and provides more comprehensive information on HCE consequences of non-compliance than mean-based regressions alone.

Degree of regional variation and effects of health insurance-related factors on the utilization of 24 diverse healthcare services - a cross-sectional study.

BACKGROUND: Regional variation in healthcare utilization could reflect unequal access to care, which may lead to detrimental consequences to quality of care and costs. The aims of this study were to a) describe the degree of regional variation in utilization of 24 diverse healthcare services in eligible populations in Switzerland, and b) identify potential drivers, especially health insurance-related factors, and explore the consistency of their effects across the services. METHODS: We conducted a cross-sectional study using health insurance claims data for the year of 2014. The studied 24 healthcare services were predominantly outpatient services, ranging from screening to secondary prevention. For each service, a target population was identified based on applicable clinical recommendations, and outcome variable was the use of the service. Possible influencing factors included patients' socio-demographics, health insurance-related and clinical characteristics. For each service, we performed a comprehensive methodological approach including small area variation analysis, spatial autocorrelation analysis, and multilevel multivariable modelling using 106 mobilité spaciale regions as the higher level. We further calculated the median odds ratio in model residuals to assess the unexplained regional variation. RESULTS: Unadjusted utilization rates varied considerably across the 24 healthcare services, ranging from 3.5% (osteoporosis screening) to 76.1% (recommended thyroid disease screening sequence). The effects of health insurance-related characteristics were mostly consistent. A higher annual deductible level was mostly associated with lower utilization. Supplementary insurance, supplementary hospital insurance and having chosen a managed care model were associated with higher utilization of most services. Managed care models showed a tendency towards more recommended care. After adjusting for multiple influencing factors, the unexplained regional variation was generally small across the 24 services, with all MORs below 1.5. CONCLUSIONS: The observed utilization rates seemed suboptimal for many of the selected services. For all of them, the unexplained regional variation was relatively small. Our findings confirmed the importance and consistency of effects of health insurance-related factors, indicating that healthcare utilization might be further optimized through adjustment of insurance scheme designs. Our comprehensive approach aids in the identification of regional variation and influencing factors of healthcare services use in Switzerland as well as comparable settings worldwide.

Need For Long-Term Care in Children is Increasingly Caused by Disorders of Psychological Development. Changes in the Care Causing Diagnoses According to German Social Code (SGB XI) Between 2009-2014.

AIM OF THE STUDY: There is an ongoing discussion on the increasing number of children with mental and developmental disorders, with some even needing long-term care according to the German Social Code XI. This study was performed to identify the main diagnoses justifying such care in children and to analyse their prevalence over time. METHODS: The diagnoses justifying long-term care were evaluated using care assessments of Bavarian children and adolescents between 2009 to 2014 by the medical service of statutory health insurance. RESULTS: Over the years investigated, the percentage of assessments due to a mental and behavioural disorder rose significantly from 36.2 to 42.2%. Since 2012, the most common diagnose changed from Down's syndrome to pervasive developmental disorders with marked increase of also mixed specific developmental disorders. In new applications for nursing insurance services the proportion of pervasive developmental disorders rose gradually from 151 in 2010 to 254 in 2014. During the whole period of time, the overall care dependency in children seemed to be stable. CONCLUSIONS: These observations might rather be influenced by altered awareness of health and illness, increasing readiness to seek help with psychological or developmental impairments as well as changed diagnostic criteria than by a steady increase in affected individuals.

Combined diffusing capacity for nitric oxide and carbon monoxide as predictor of bronchiolitis obliterans syndrome following lung transplantation.

BACKGROUND: There is a need for non-invasive parameters that are sensitive to the development of the bronchiolitis obliterans syndrome (BOS) in lung transplantation (LTx) patients. We studied whether the pulmonary diffusing capacity for inhaled nitric oxide is capable of detecting BOS stages. METHODS: Sixty-one LTx patients were included into this cross-sectional study (19/29/7/3/3 in BOS stages 0/0-p/1/2/3). For analysis stages 0/0-p versus 1/2/3 ("BOS binary-early"), and stages 0/0-p/1 versus 2/3 ("BOS binary-late") were summarized. Measurements of the combined diffusing capacity for nitric oxide (DLNO) and carbon monoxide (DLCO) were compared with spirometry and bodyplethysmography, and their relative importance was evaluated by discriminant analysis. RESULTS: Regarding the recognition of "BOS binary-early", among spirometric parameters forced expiratory volume in 1 s (FEV1) was best, among bodyplethysmographic parameters airway resistance, and among diffusing parameters DLNO. Regarding "BOS binary-late", DLNO was inferior to bodyplethysmographic parameters. CONCLUSION: Although the study comprised only measurements at a single time point and no follow-up, DLNO outperformed FEV1, the time course of which is used in detecting BOS. Together with its pathophysiological plausibility, this result suggests that the measurement of DLNO, possibly over time, could be an easily applicable tool for the monitoring of LTx patients and should be evaluated in larger studies.

Acute effects of combined exercise and oscillatory positive expiratory pressure therapy on sputum properties and lung diffusing capacity in cystic fibrosis: a randomized, controlled, crossover trial.

BACKGROUND: Regular airway clearance by chest physiotherapy and/or exercise is critical to lung health in cystic fibrosis (CF). Combination of cycling exercise and chest physiotherapy using the Flutter® device on sputum properties has not yet been investigated. METHODS: This prospective, randomized crossover study compared a single bout of continuous cycling exercise at moderate intensity (experiment A, control condition) vs a combination of interval cycling exercise plus Flutter® (experiment B). Sputum properties (viscoelasticity, yield stress, solids content, spinnability, and ease of sputum expectoration), pulmonary diffusing capacity for nitric oxide (DLNO) and carbon monoxide (DLCO) were assessed at rest, directly and 45 min post-exercise (recovery) at 2 consecutive visits. Primary outcome was change in sputum viscoelasticity (G', storage modulus; G", loss modulus) over a broad frequency range (0.1-100 rad.s- 1). RESULTS: 15 adults with CF (FEV1range 24-94% predicted) completed all experiments. No consistent differences between experiments were observed for G' and G" and other sputum properties, except for ease of sputum expectoration during recovery favoring experiment A. DLNO, DLCO, alveolar volume (VA) and pulmonary capillary blood volume (Vcap) increased during experiment A, while DLCO and Vcap increased during experiment B (all P < 0.05). We found no differences in absolute changes in pulmonary diffusing capacity and its components between experiments, except a higher VA immediately post-exercise favoring experiment A (P = 0.032). CONCLUSIONS: The additional use of the Flutter® to moderate intensity interval cycling exercise has no measurable effect on the viscoelastic properties of sputum compared to moderate intensity continuous cycling alone. Elevations in diffusing capacity represent an acute exercise-induced effect not sustained post-exercise. TRIAL REGISTRATION: ClinicalTrials.gov; No.: NCT02750722 ; URL: clinical.trials.gov; Registration date: April 25th, 2016.

Human-biomonitoring and individual soil measurements for children and mothers in an area with recently detected mercury-contaminations and public health concerns: a cross-sectional study.

In this study, we assessed intracorporal mercury concentrations in subjects living on partially mercury-contaminated soils in a defined area in Switzerland. We assessed 64 mothers and 107 children who resided in a defined area for at least 3 months. Mercury in biological samples (urine and hair) was measured, a detailed questionnaire was administered for each individual, and individual mercury soil values were obtained. Human biomonitoring results were compared with health-related and reference values. Mothers and children in our study had geometric means (GMs) of 0.22 µg Hg/g creatinine in urine (95th percentile (P95) = 0.85 µg Hg/g) and 0.16 µg Hg/g (P95 = 0.56 µg Hg/g), respectively. In hair, mothers and children had GMs of 0.21 µg Hg/g (P95 = 0.94 µg/g) and 0.18 µg/g (P95 = 0.60 µg/g), respectively. We found no evidence for an association between mercury values in soil and those in human specimens nor for a health threat in residential mothers and children.

Can serum cytokine profile discriminate irritant-induced and allergen-induced symptoms? A cross-sectional study in workers mostly exposed to laboratory animals.

BACKGROUND: In workers exposed mostly to laboratory animals (LA), symptoms may be due to irritants or allergens. Correct aetiological diagnosis is important for health surveillance. OBJECTIVES: This study aims to test whether work-related (WR) allergen-induced symptoms are associated with a cytokine profile distinct from that due to irritants. METHODS: In a cross-sectional study (n=114), WR respiratory and/or skin symptoms were assessed through a standardised clinical examination and sensitisation to rat and/or mouse allergen determined by serum immunoglobulin E. Serum cytokine concentrations were measured by multiplex assays. The predefined cytokine profiles 'sensitiser' (interleukin (IL)-4, IL-5, IL-13, eotaxin-1) and 'irritation' (IL-8, IL-17A, IL-17F, IL-22) were considered positive, when ≥3 concentrations exceeded the 95th percentile of the asymptomatic non-sensitised group. Results were examined by hierarchical clustering analyses (HCA) and multiple linear regression. Explorative analyses were carried out for nine additional cytokines. Exposure to allergens and endotoxin was assessed in a subpopulation. RESULTS: The prevalence of the profile 'irritation' was comparable in 28 symptomatic non-sensitised workers and 71 asymptomatic non-sensitised workers. HCA showed that nearly all symptomatic non-sensitised workers were gathered in two subclusters, characterised by high IL-17A levels, but different IL-8 levels. Multiple linear regression identified drug consumption and current complaints as confounders. Sensitised subjects were too few (n=14) for testing the profile 'sensitiser'. CONCLUSIONS: In this unselected population of LA workers, the profile 'irritation' did not prove to be a valuable health surveillance tool. Low power precluded assessment of the profile 'sensitiser'. The increased IL-17A concentration may originate from irritative constituents of organic dust.

Respiratory allergies among veterinarians: two cross-sectional surveys from 2006 to 2012.

PURPOSE: Animal-related allergy is known to be an occupational hazard among veterinarians; however, there is a lack of data showing to which extent these are affected. We aimed at describing the prevalence of respiratory allergies in this population. METHODS: In two repeated cross-sectional surveys in 2006 and 2012 in Bavaria, we examined the prevalence of wheezing, asthma and allergic rhinitis by questionnaires. We additionally performed multiple regression analysis to identify associated factors. RESULTS: Overall participation rate was above 60%, leading to sample sizes of 512 in 2006 and 596 in 2012, respectively. Prevalences of allergic symptoms ranged from 5.1 to 5.6% for asthma, 17.0 to 20.2% for rhinitis, and 11.4 to 14.3% for wheezing, as well as 7.2 to 11.3% for wheezing without having a cold. The percentage of women in this occupation grew between the first and second survey. There were gender differences in both surveys concerning age and practice type (p < 0.0001). Women had a lower mean age (42.1 vs. 53.0 years in 2012) and worked much more often exclusively with small animals (50.2 vs. 15.9% in 2012). There was a borderline significantly higher prevalence for allergic rhinitis in women than in men in 2012 (20.1 vs. 13.7, p = 0.052). Having allergic rhinitis was clearly associated with wheezing, wheezing without cold and asthma. CONCLUSIONS: In a repeated cross-sectional survey at an interval of 6 years among veterinarians, we found a relatively stable overall prevalence of wheeze, wheeze without having a cold, asthma and allergic rhinitis.

Cadmium or cadmium compounds and chronic kidney disease in workers and the general population: a systematic review.

BACKGROUND: Cadmium (Cd) is abundantly documented as a metal mainly affecting tubular function both in workers and in the general population indirectly exposed via the environment. Results from epidemiological studies linking Cd exposure and risk of progression to chronic kidney disease (CKD) are, however, conflicting. OBJECTIVES: To perform a systematic review of the association between Cd exposure and CKD. METHODS: A systematic appraisal of publications found in MEDLINE (1946-2014), EMBASE (1974-2012) and an in-house database (1986-2013) was conducted. Additional studies were searched for by contacting experts and checking reference lists. Search terms used key and text words. No language restriction was applied. Cohort, case-control and case-series with follow-up including individual and objective assessment of occupational or environmental exposure were eligible. Studies were selected and data extracted by two independent reviewers using predefined forms. Study characteristics and results were extracted to structured tables. Synthesis was qualitative and results appraised with causality criteria. RESULTS: Thirty-four exposed groups, totaling more than 3000 participants, were eligible. Overall, results disclosed no convincing evidence supporting a risk of progression to CKD in populations exposed to Cd. Lack of information about methods, risk of bias and heterogeneity were identified as limitations and precluded conducting a meta-analysis. Publication bias did not appear as a major problem. CONCLUSIONS: This qualitative systematic review does not support the contention that human exposure to Cd leads to progressive CKD.

Evaluation of breeding strategies for polledness in dairy cattle using a newly developed simulation framework for quantitative and Mendelian traits.

BACKGROUND: Intensified selection of polled individuals has recently gained importance in predominantly horned dairy cattle breeds as an alternative to routine dehorning. The status quo of the current polled breeding pool of genetically-closely related artificial insemination sires with lower breeding values for performance traits raises questions regarding the effects of intensified selection based on this founder pool. METHODS: We developed a stochastic simulation framework that combines the stochastic simulation software QMSim and a self-designed R program named QUALsim that acts as an external extension. Two traits were simulated in a dairy cattle population for 25 generations: one quantitative (QMSim) and one qualitative trait with Mendelian inheritance (i.e. polledness, QUALsim). The assignment scheme for qualitative trait genotypes initiated realistic initial breeding situations regarding allele frequencies, true breeding values for the quantitative trait and genetic relatedness. Intensified selection for polled cattle was achieved using an approach that weights estimated breeding values in the animal best linear unbiased prediction model for the quantitative trait depending on genotypes or phenotypes for the polled trait with a user-defined weighting factor. RESULTS: Selection response for the polled trait was highest in the selection scheme based on genotypes. Selection based on phenotypes led to significantly lower allele frequencies for polled. The male selection path played a significantly greater role for a fast dissemination of polled alleles compared to female selection strategies. Fixation of the polled allele implies selection based on polled genotypes among males. In comparison to a base breeding scenario that does not take polledness into account, intensive selection for polled substantially reduced genetic gain for this quantitative trait after 25 generations. Reducing selection intensity for polled males while maintaining strong selection intensity among females, simultaneously decreased losses in genetic gain and achieved a final allele frequency of 0.93 for polled. CONCLUSIONS: A fast transition to a completely polled population through intensified selection for polled was in contradiction to the preservation of high genetic gain for the quantitative trait. Selection on male polled genotypes with moderate weighting, and selection on female polled phenotypes with high weighting, could be a suitable compromise regarding all important breeding aspects.