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Background: Fear of progression (FoP) is a reactive, conscious concern about chronic disease progression and its consequences which may limit quality of life substantially. Only one study has examined FoP in Parkinson’s disease (PD), showing the second highest FoP scores among chronic diseases. Objective: To examine FoP prevalence and to exploratorily analyze determinants of FoP in PD. Methods: Within a multicenter cross-sectional study, 120 PD inpatients (age: 64.45±9.20; 60.8% male; UPDRS-III: 28.86±16.12) were examined with the FoP questionnaire (FoP-Q; max. 20 points). Stepwise multiple linear regression analysis examined sociodemographic, clinical, and (neuro-) psychological determinants of FoP. Results: With a mean FoP-Q score of 8.08±2.17, 63.0% of the patients were classified with moderate FoP and 17.6% with dysfunctional (i.e., severe) FoP. The highest scores were shown for the subscale ‘loss of autonomy’. Increased levels of anxiety, less self-efficacy, female gender, current employment, and lower health literacy were identified as significant determinants associated with FoP. Conclusion: With more than 80% of patients showing moderate to dysfunctional FoP, it must be regarded as a frequent symptom in PD, which needs to be further understood and addressed in clinical practice. Clinical parameters like PD duration and severity were no determinants for FoP, indicating that FoP awareness must be considered by professionals at all disease stages.

Objective Fatigue in multiple sclerosis (MS) is common, burdensome, and usually assessed by self-report measures. This retrospective data analysis of the twice-daily Alertness test (Test battery of Attentional Performance) examined the extent to which this assessment procedure is associated with MS-related fatigue. Method Two-hundred and thirteen German inpatients (136 women) aged 18–69 years with predominantly relapsing MS (72.8%) were included. Based on reaction time (RT) differences between morning tonic alertness (8:30–11:00 a.m.) and afternoon tonic alertness (3:00–4:30 p.m.), patients were divided into an “improver,” “maintainer,” or “decliner” group. Multinomial logistic regression (MLR) was calculated to predict the likelihood of belonging to one of these performance groups, taking into account cognitive fatigue (Fatigue Scale of Motor and Cognition, FSMCcog), disease severity (Expanded Disability Status Scale, EDSS), depression (Center for Epidemiologic Studies Depression Scale, CES-D), gender, and tonic alertness (a.m.). Results The final MLR model (R2 = .30) included tonic alertness (a.m.) ( Conclusions These results show a relationship between subjective fatigue and tonic alertness. However, other variables also contribute to this association, suggesting that the RT differences between twice-daily measures of tonic alertness is not related to increased subjective fatigue in a substantial number of pwMS, which diminishes the diagnostic value. Further studies including relevant variables such as sleepiness are urgently needed.

Zusammenfassung. Multiple Sklerose (MS) kann bereits in der mittleren Lebensphase (36 bis 55 Jahre) die berufliche Teilhabe entscheidend beeinflussen. Diese Studie untersuchte, inwieweit sich 86 MS-Erkrankte mit unterschiedlicher beruflicher Leistungseinstufung bezüglich ausgewählter Studienvariablen zum Zeitpunkt der Fragebogenerhebung (T1) und der stationären Entlassung (T0) unterschieden. Die Gesamtstichprobe zeigte leichtgradige kognitive Dysfunktionen und ausgeprägte Fatiguewerte. Mittels logistischer Regressionsanalysen prädizierten die Variablen Tonische Alertness (TAP), Motorische Fatigue (FSMC), Expanded Disability Status Scale (EDSS) und Cognitive Reserve Index questionnaire (CRIq; CRI-Arbeit) die Leistungsbeurteilung bei T0 zu 71 %. Den Variablen Krankheitsdauer, Motorische Fatigue, Selbstwirksamkeit (FERUS) und Neuropsychologischer Störungsindex gelang dies zu 67 % bei T1. Die Studienergebnisse zeigen, dass motorische Fatigue und (spezifische und globale) neuropsychologische Marker ein relevantes Erklärungspotenzial hinsichtlich der Erwerbseinstufung von MS-Erkrankten besitzen. Zudem scheint die Selbstwirksamkeit die Erwerbsfähigkeit positiv zu beeinflussen.

Background: Diesel engine exhaust causes adverse health effects. Meanwhile, the impact of renewable diesel exhaust on human health is less known. In this study, nasal patency, pulmonary function, and self-rated symptoms were assessed in 19 healthy volunteers after two separate 3-hour exposures to renewable diesel (hydrotreated vegetable oil [HVO]) exhaust, and exposure to filtered air (FA) for comparison. The HVO exposures were generated with two modern non-road vehicles (2019) having either: 1) no aftertreatment system (HVOPM+NOx), or 2) an aftertreatment system containing a diesel oxidation catalyst and a diesel particulate filter (HVONOx). The exposure concentrations complied with current EU occupational exposure limits (OELs) of NO, NO2, formaldehyde, polycyclic aromatic hydrocarbons (PAHs), and future OELs of elemental carbon (EC) from 2023. Results: Exposure to HVOPM+NOx consisted of PM1 (≈90 µg m-3, 54 µg m-3 EC) and NOx (NO 3.4 ppm, NO2 0.6 ppm). The average total respiratory tract deposition of PM1 was 27 µg h-1. The deposition fraction of HVO PM1 was 40-50% higher compared to diesel exhaust PM1 from an older vehicle, due to smaller particle sizes of the HVOPM+NOx exhaust. Exposure to HVONOx consisted mainly of NOx (NO 2.0 ppm, NO2 0.7 ppm) with low level of PM1 (~1 µg m-3). Compared to filtered air, exposure to HVOPM+NOx and HVONOx caused higher incidence of self-reported symptoms (78%, 63%, respectively, vs. 28% for FA, pPM+NOx showed 40-50% higher eye and throat irritation symptoms. Compared to filtered air, a decrement in nasal patency was found for the HVONOx exposures (-18.1, 95%CI: -27.3 to -8.8 L min-1), and for the HVOPM+NOx (-7.4 (-15.6 to 0.8) L min-1). Overall, no change was indicated in the pulmonary function tests (spirometry, peak expiratory flow, forced oscillation technique), except a slight increase in FEV1/FVC after exposure to HVONOx.Conclusion: Short-term exposure to HVO exhaust below the EU OELs did not cause severe pulmonary function changes in healthy subjects. However, an increase in self-rated mild irritation symptoms, and mild decrease in nasal patency after two HVO exposures may indicate irritative effects from exposure to HVO exhaust from modern non-road vehicles below future OELs.

Contains fulltext : 234215.pdf (Publisher’s version ) (Closed access) Background: Most neglect treatment studies focus on automatic re-orientation procedures, assuming a deficit in automatic processes. We compare an automatic- and a controlled procedure, using the endogenous and exogenous variants of Posner's covert shift of attention task. Method: In two experiments, neglect patients and patients with a right hemispherical stroke without neglect performed three blocks of Posner's covert shift of attention task (Posner Task) on two days. In Study 1 we used endogenous cues, in Study 2, exogenous cues. Results: In the endogenous task, neglect patients improved significantly with valid left-sided cues between block 1 and 2 on Day 1, subsequently showing a plateauing. They also showed a gradual improvement on invalid trials on both days. In the exogenous condition, all participants responded only increasingly faster on trials with a long stimulus onset asynchrony. Practicing on both tasks led to fewer omissions for left-sided targets, minimally in the exogenous and clearly in the endogenous condition. Conclusion: In line with prior neuroanatomical studies, our study shows that practicing an endogenous, but not an exogenous, visuospatial attention task leads to significant improvements in neglect patients, especially for invalid trials, suggesting that neglect treatments based on top-down strategies should be given more attention. 9 p.

BackgroundControversy exists as to the health effects of exposure to asphalt and crumb rubber modified (CRM) asphalt, which contains recycled rubber tyres.ObjectiveTo assess exposures and effects on airway symptoms, lung function and inflammation biomarkers in conventional and CRM asphalt road pavers.Methods116 conventional asphalt workers, 51 CRM asphalt workers and 100 controls were investigated. A repeated-measures analysis included 31 workers paving with both types of asphalt. Exposure to dust, nitrosamines, benzothiazole and polycyclic aromatic hydrocarbon (PAH) was measured in worksites. Self-reported symptoms, spirometry test and blood sampling were conducted prework and postwork. Symptoms were further collected during off-season for asphalt paving.ResultsDust, PAHs and nitrosamine exposure was highly varied, without difference between conventional and CRM asphalt workers. Benzothiazole was higher in CRM asphalt workers (pConclusionCRM asphalt workers are exposed to higher benzothiazole. Further studies are needed to identify the source of nitrosamines in conventional asphalt. Mild decrease in lung function in CRM asphalt workers and work-related eye symptoms in both asphalt workers were observed. However, our study did not find strong evidence for severe respiratory symptoms and inflammation response among asphalt workers.

Purpose Welders are exposed to airborne particles from the welding environment and often develop symptoms work-related from the airways. A large fraction of the particles from welding are in the nano-size range. In this study we investigate if the welders’ airways are affected by exposure to particles derived from gas metal arc welding in mild steel in levels corresponding to a normal welding day. Method In an exposure chamber, 11 welders with and 10 welders without work-related symptoms from the lower airways and 11 non-welders without symptoms, were exposed to welding fumes (1 mg/m3) and to filtered air, respectively, in a double-blind manner. Symptoms from eyes and upper and lower airways and lung function were registered. Blood and nasal lavage (NL) were sampled before, immediately after and the morning after exposure for analysis of markers of oxidative stress. Exhaled breath condensate (EBC) for analysis of leukotriene B4 (LT-B4) was sampled before, during and immediately after exposure. Results No adverse effects of welding exposure were found regarding symptoms and lung function. However, EBC LT-B4 decreased significantly in all participants after welding exposure compared to filtered air. NL IL-6 increased immediately after exposure in the two non-symptomatic groups and blood neutrophils tended to increase in the symptomatic welder group. The morning after, neutrophils and serum IL-8 had decreased in all three groups after welding exposure. Remarkably, the symptomatic welder group had a tenfold higher level of EBC LT-B4 compared to the two groups without symptoms. Conclusion Despite no clinical adverse effects at welding, changes in inflammatory markers may indicate subclinical effects even at exposure below the present Swedish threshold limit (8 h TWA respirable dust).

Approximately 16 % of adult onset asthma is caused by occupational exposure. The need for early detection of irritant caused asthma is key in treating and preventing the progression of the disease. The aim of the work was to investigate if exposure to irritants cause change in gas composition in exhaled breath, the “exhalome”. We studied 15 female hairdressers exposed to a controlled dose of aerosolized bleach powder in a sealed climate chamber. The subjects’ self-reported symptoms, spirometry and gas components were monitored. The exhalome was collected for breath holding times of 2 and 10 seconds from central (400 ml) and peripheral lung (1500 ml), once prior to and twice after exposure. Thus, subjects were their own controls. The composition of the gas was analyzed using a Proton Transfer Reaction – Time of Flight – Mass Spectrometer (PTR-ToF-MS) where volatile organic compounds of mass up to 253 atomic mass units are identified with high time resolution. Preliminary analysis of the data shows a variation of the concentrations of the different gases in exhalome over the course of the day and that levels of isoprene and acetone are higher for longer breath holding time. More analysis is needed to evaluate if the technique is able to detect differences in the exhalome caused by the exposure. Detailed information on the relationships between the exhalome and inflammation processes in the respiratory tract induced by irritants is also required. This may contribute to a deeper understanding of asthma. In the future a PTR-ToF-MS could potentially be used as a real-time non-invasive tool for early detection asthma in exposed workers.

Objective Fatigue and cognitive deficits are frequent symptoms of multiple sclerosis (MS). However, the exact nature of their co-occurrence is not fully understood. We sought to determine the impact of cognitive and physical fatigue on subjective cognitive deficits in MS patients and healthy controls. Methods Self-reports of fatigue (FSMC), depression (CES-D), cognitive deficits (CFQ), and personality traits (NEO-FFI, ANPS) among 30 MS inpatients and 30 healthy controls were analyzed using hierarchical regression models. The frequency of cognitive mistakes was used as the dependent variable and the extent of cognitive and physical fatigue as the independent variable. Results Cognitive fatigue was the only unique and significant predictor of cognitive mistakes in both groups, explaining 13.3% of additional variance in the MS group after correcting for age, mood, and physical fatigue. Physical fatigue had no significant impact on cognitive mistakes. While age had an impact on cognitive mistakes and depression in healthy controls, this association was not significant in MS patients. Depression was significantly correlated with cognitive mistakes and cognitive fatigue in MS patients. Conclusions The interplay of cognitive fatigue and subjective cognitive impairment can be generalized, with the exception of the variables of age and depression, which were shown to have differing impacts on cognitive mistakes in MS patients and healthy controls, respectively. Cognitive fatigue was linked to cognitive mistakes even after correcting for overlapping items in MS patients only. Future research should further investigate the link between cognitive fatigue and attention lapses in daily life by using various objective assessments.

Objective: Hairdressers have an increased risk for airway symptoms especially when using hair-bleaching powder containing persulfate. To minimize exposure, dust-free bleaching powder (DFP) has been made available. We studied the effects of regular powder (RP) or DFP on the airway symptoms of hairdressers with hair-bleaching associated rhinitis. Methods: Twelve hairdressers each performed three hair-bleachings on a wig in an exposure chamber. Half of the subjects used RP and half used DFP. Exposure to persulfate and ammonia was measured. Before and after each bleaching, the participants stated their degree of airway symptoms on a visual analogue scale. Nasal lavage and blood were sampled before exposure, after the last bleaching, and in the morning after exposure to measure inflammatory markers. Results: Exposure to persulfate was higher when using RP compared to DFP, 22 (11-55) vs. 12 (8-13) μg/m3; median (min-max). Exposure to ammonia did not differ between the groups. Both groups reported an increase in asthma-like symptoms and this increase was significant. Neutrophils, lymphocytes, and monocytes increased after exposure in both groups; monocytes decreased the day after. In nasal lavage, IL-8 was increased the morning after for both types of powder, and the increase was significant in the total group. IL-6 increased immediately after exposure and the day after only in the group using RP. Conclusions: Although DFP powder emits lower levels of persulfate, effects are still elicited in symptomatic hairdressers.

Phthalates are ubiquitous in indoor environments, which raises concern about their endocrine-disrupting properties. However, studies of human uptake from airborne exposure are limited. We studied the inhalation uptake and dermal uptake by air-to-skin transfer with clean clothing as a barrier of two deuterium-labeled airborne phthalates: particle-phase D4-DEHP (di(2-ethylhexyl)phthalate) and gas-phase D4-DEP (diethyl phthalate). Sixteen participants, wearing trousers and long-sleeved shirts, were under controlled conditions exposed to airborne phthalates in four exposure scenarios: dermal uptake alone and combined inhalation + dermal uptake of both phthalates. The results showed an average uptake of D4-DEHP by inhalation of 0.0014 ± 0.00088 (μg kg–1 bw)/(μg m–3)/h. No dermal uptake of D4-DEHP was observed during the 3 h exposure with clean clothing. The deposited dose of D4-DEHP accounted for 26% of the total inhaled D4-DEHP mass. For D4-DEP, the average uptake by inhalation + dermal was 0.0067 ± 0.0045 an...

Purpose We aimed to follow diary-registered symptoms from eyes and airways in mild steel welders and relate them to different exposure measures. Furthermore, we would clarify the influence of possible effect modifiers. Methods Non-smoking welders with (N = 74) and without (N = 32) work-related symptoms the last month were enroled. Symptoms and work tasks each day for three two-week periods during 1 year were obtained. Respirable dust (RD) was measured 1 day each period for each worker. The personal daily exposure was assessed as: (1) days at work, (2) welding time and (3) estimates of RD from welding and grinding, calculated from diary entries and measurements. Results Only 9.2 % of the particle measurements exceed the Swedish occupational exposure limit (OEL; 5 mg/m3). Days at work increased the risk of symptoms studied: eyes: 1.79 (1.46–2.19), nasal: 2.16 (1.81–2.58), dry cough: 1.50 (1.23–1.82) and wheezing and/or dyspnoea: 1.27 (1.03–1.56; odds ratio, 95 % confidence interval). No clear dose–response relationships were found for the other exposure estimates. Eye symptoms increased by number of years welding. Nasal symptoms and dry cough increased having forced expiratory volume in first second below median at baseline. Wheezing and/or dyspnoea increased in winter, by number of years welding, having a negative standard skin-prick test and having a vital capacity above median at baseline. Conclusion The current Swedish OEL may not protect welders against eye and airway symptoms. The results add to the evidence that welders should be offered regular medical surveillance from early in the career.

Background: Airborne particles are associated with increased morbidity and mortality due to respiratory and cardiovascular diseases in polluted areas. There is a growing interest in nano-sized particles with diameter < 100 nm and their potential health effects. Heart rate variability (HRV) is a noninvasive method for cardiovascular risk prediction in high prevalent groups. Aim of study: The aim was to evaluate the impact of nano-sized indoor air particles on HRV for healthy and adult females. Methods: All exposures were performed as controlled chamber experiments with particle exposure from burning candles, terpene + ozone reactions or filtered air in a double-blind cross over design. Twenty-two healthy females were investigated during 10 min periods at different exposures and the reactivity in high frequency (HF) spectral band of HRV were computed. Results: Heart rate was unchanged from baseline values in all groups during all experimental settings. HF power of HRV tended to increase during exposure to particles from burning candle while particles from terpene + ozone reactions tended to decrease HF power. Conclusions: Exposure to nano-sized particles of burning candles or terpene + ozone reactions results in different patterns of heart rate variability, with signs of altered autonomic cardiovascular control. Practical implications: This study indicates that the HRV method may be used for information on physiological responses of exposure to different nano-sized particles and contribute to the understanding of mechanisms behind health effects of particle exposures. (C) 2014 The Authors. Published by Elsevier Ltd.

Objectives: Hairdressers have several work-related health hazards. Little is known of their strategies for the work environment. The aim of this study was to explore female hairdressers' own views on their physical, social and psychological work environment as possibilities of influencing it, implementation of their knowledge, financial impacts and how work-related symptoms affect their views. Methods: Fourteen hairdressers working for four years were subjected to open-ended interviews covering aspects of the physical, social and psychological work environment. Content analysis was applied. Results: An awareness of the impact of the work environment and the possibilities of influencing it emerged, but also an inability to achieve preventive improvements. This included reflections concerning ventilation, health issues, job strain, hair products, financial issues, knowledge from school and concern for having to leave the profession. The organization and acceptance of the work environment were important issues. Making the work environment an active part of their business was not common. Conclusions: Female hairdressers had an awareness of their work environment but lacked the means and strategies to make it an active part of their business. The main focus was on the customers and the work techniques. Having various symptoms did not alter this. Organizational and financial issues could put limitations on the work environment. Teachers were crucial in making the work environment interesting. Hairdressing was seen with advantages and disadvantages, and its future was seen as being insecure in terms of the occupational health risks. The hairdressers expressed a great pride in their profession providing possibilities for development. (Less)

In den Naturwissenschaften hat durch die Systemtheorie und die Berücksichtigung von Komplexität, Zirkularität und Prozessualität seit langem ein Paradigmenwechsel stattgefunden. Dieses systemtheoretische Denken bildet das Fundament der heutigen Systemischen Therapie (ST). Ihr besonderes Merkmal ist die Einbeziehung des interaktionellen Kontextes unter Beachtung unterschiedlicher Systemebenen (Patient, Familie, Behandlungsteam usw.). Das Aufgabengebiet der klinischen Neuropsychologie umfasst wiederum nicht nur die Diagnostik und Therapie gestörter Hirnfunktionen, sondern der „gesamte Patient” und seine Angehörigen stehen im Behandlerfokus; dies erfordert ein entsprechend aufgestelltes Interventionsrepertoire. Gemäß Autorenmeinung kann die ST diesen „neuropsychologischen Behandlungskoffer” mit ihrem Grundverständnis, ihrer Haltung und ihrem Methodenspektrum bereichern. Im Blickpunkt stehen dabei die „kommunikativen Spielregeln” (Sinndeutungen, Sprache, Interaktionsmuster, Rollenverteilungen), die infolge eines Krankheitsereignisses bei Patienten, Angehörigen und Rehabilitationsteam „systemdynamisch” verändert sein können.

in Undetermined The aim of this study was to achieve a method to perform detailed characterization and human exposure studies of nanosized and nanostructured aerosol particles. The source chosen was mild steel, active gas, arc welding fume. The setup consisted of a generation chamber, where welding can be performed, connected to an airtight stainless steel 22 m(3) exposure chamber. Instrumentation, consisting of a tapered element oscillating microbalance, a scanning mobility particle sizer, and a sampler for electron microscopy and particle-induced X-ray emission analysis was connected to the stainless steel chamber. The feasibility of the system for human exposure studies was evaluated by exposing 31 human volunteers, in groups of three, to a test aerosol containing 1 mg/m(3) welding fumes and to conditioned, filtered air. The results show that an aerosol that accurately represents dilute welding fume exposures that occur in workplaces can be produced in a controlled manner, and that the experimental setup can be used for 6 h, double-blind, exposures of human subjects. Particle mass concentration levels could be varied from

Background There is a controversy on exposure and adverse health effects of workers working with road asphalt paving. Furthermore, the increasing usage of crumb rubber modified (CRM) asphalt raises the concern of exposure to CRM asphalt. Objective To assess the exposure of both conventional and CRM asphalt, and to elucidate the health effects regarding airway symptoms, lung function, inflammation response and genotoxic effects on telomere length (TL) and mitochondria DNA copy number (mtDNAcn). Methods We carried out a cross-week study with 116 workers with conventional asphalt, 51 workers with CRM asphalt and 100 controls in Sweden. Personal air sampling was carried out in 60 workers in varied worksites. Symptoms during working week were investigated by standard questionnaires. Lung function test results together with urine and blood samples were collected before work on Monday morning and immediately after work on Thursday afternoon. Results The exposure level for benzothiazol was higher in CRM asphalt (2.2 ± 0.8 µg/m3) than conventional asphalt (0.7 ± 0.8 µg/m3, p Conclusion The results do not indicate that road asphalt paving in open area is an occupation with high exposure or severe health issues. Similarly, the results do not suggest that CRM asphalt is related to more adverse health effects than conventional asphalt. However, the higher concentration of benzothiazole during CRM paving may suggest that crumb rubber is a main source and that benzothiazole may be useful as an indicator of CRM fume exposure.

OBJECTIVES: Hairdressers often complain of work-related rhinitis (WR). They are infrequently sensitized to persulphates. The cause and mechanism of the symptoms and the effects on their health-related quality of life (HRQoL) remains unclear. The objectives were to follow female hairdressers with WR mainly from bleaching powder regarding nasal reactivity to persulphate and to evaluate symptoms, HRQoL and inflammatory markers in nasal lavage during a working period after vacation and compared with hairdressers without symptoms and pollen allergic women. METHODS: Skin prick tests to persulphate were performed in the hairdressers. Participants kept a diary of symptoms and of work tasks (hairdressers only). They completed HRQoL questionnaires. Eosinophil cationic protein (ECP) in nasal lavage fluid was examined. The symptomatic hairdressers performed nasal challenges with persulphate before and after the exposure. RESULTS: Skin prick tests were negative. Although the nasal reactivity to persulphate did not change a steady increase in nasal symptoms, especially blockage, and in ECP was noticed in the symptomatic hairdressers. The HRQoL deteriorated in the symptomatic hairdressers indicating an effect on their working situation and daily life. The atopics had more, but varying symptoms (itching, sneezing and secretion). CONCLUSIONS: The difference in the clinical picture between the symptomatic hairdressers and the pollen allergic women, the increase in symptoms and ECP in the nasal lavage support the view that a sensitization to hairdresser chemicals by a mechanism not yet understood is operating. The deterioration of the HRQoL in the symptomatic hairdressers indicates a considerable effect on their life.

Phthalate esters are suspected endocrine disruptors that are found in a wide range of applications. The aim of this study was to determine the excretion of urinary metabolites in 16 individuals after inhalation and/or dermal exposure to 100&ndash, 300 &micro, g/m3 of deuterium-labelled diethyl phthalate (D4-DEP) and bis(2-ethylhexyl) phthalate (D4-DEHP). Dermal exposure in this study represents a case with clean clothing acting as a barrier. After inhalation, D4-DEP and D4-DEHP metabolites were excreted rapidly, though inter-individual variation was high. D4-DEP excretion peaked 3.3 h (T&frac12, of 2.1 h) after combined inhalation and dermal exposure, with total excreted metabolite levels ranging from 0.055 to 2.351 nmol/nmol/m3 (nmol of urinary metabolites per phthalates air concentration in (nmol/m3)). After dermal exposure to D4-DEP, metabolite excretion peaked 4.6 h (T&frac12, of 2.7 h) after exposure, with excreted metabolite levels in between 0.017 and 0.223 nmol/nmol/m3. After combined inhalation and dermal exposure to D4-DEHP, the excretion of all five analysed metabolites peaked after 4.7 h on average (T&frac12, of 4.8 h), and metabolite levels ranged from 0.072 to 1.105 nmol/nmol/m3 between participants. No dermal uptake of particle phase D4-DEHP was observed. In conclusion, the average excreted levels of metabolites after combined inhalation and dermal exposure to D4-DEP was three times higher than after combined exposure to D4-DEHP, and nine times higher than after dermal exposure of D4-DEP. This study was made possible due to the use of novel approaches, i.e., the use of labelled phthalate esters to avoid the background concentration, and innovative technique of phthalate generation, both in the particle and the gas phase.

To identify changes in gene expression in the airways among welders, with and without lower airway symptoms, working in black steel. Included were 25 male, non-smoking welders. Each welder was sampled twice; before exposure (after vacation), and after 1 month of exposure. From the welders (14 symptomatic, of whom 7 had asthma-like symptoms), RNA from induced sputum was obtained for gene expression analysis. Messenger RNA from a subset of the samples (n = 7) was analysed with microarray technology to identify genes of interest. These genes were further analysed using quantitative PCR (qPCR; n = 22). By comparing samples before and after exposure, the microarray analysis resulted in several functional annotation clusters: the one with the highest enrichment score contained “response to wounding”, “inflammatory response” and “defence response”. Seven genes were analysed by qPCR: granulocyte colony-stimulating factor 3 receptor (CSF3R), superoxide dismutase 2, interleukin 8, glutathione S-transferase pi 1, tumour necrosis factor alpha-induced protein 6 (TNFAIP6), interleukin 1 receptor type II and matrix metallopeptidase 25 (MMP25). Increased levels of CSF3R, TNFAIP6 and MMP25 were indicated among asthmatic subjects compared to non-symptomatic subjects, although the differences did not reach significance. Workers’ exposure to welding fumes changed gene expression in the lower airways in genes involved in inflammatory and defence response. Thus, microarray and qPCR technique can demonstrate markers of exposure to welding fumes and possible disease-related markers. However, further studies are needed to verify genes involved and to further characterise the mechanism for welding fumes-associated lower airway symptoms.

Hairdressers are frequently exposed to bleaching powder containing persulfates, a group of compounds that may induce hypersensitivity in the airways. The mechanism causing this reaction is not clear. The aim of this study was to identify changes in the nasal lavage fluid proteome after challenge with potassium persulfate in hairdressers with bleaching powder-associated rhinitis. Furthermore, we aimed to compare their response to that of hairdressers without nasal symptoms, and atopic subjects with pollen-associated nasal symptoms. To study the pathogenesis of persulfate-associated rhinitis, the response in protein expression from the upper airway was assessed by time-dependent proteomic expression analysis of nasal lavage fluids. Samples were prepared by pooling nasal lavage fluids from the groups at different time points after challenge. Samples were depleted of high-abundant proteins, labeled with iTRAQ and analyzed by online 2D-nanoLC-MS/MS. Differences in the protein pattern between the three groups were observed. Most proteins with differentially expressed levels were involved in pathways of lipid transportation and antimicrobial activities. The major finding was increased abundance of apolipoprotein A-1, 20 min postchallenge, detected solely in the group of symptomatic hairdressers. Our results suggest there may be differences between the mechanisms responsible for the rhinitis in the symptomatic and atopic group.

Methylhexahydrophthalic anhydride (MHHPA) is a reactive, low molecular weight chemical used in products such as plastics, paints, and electronic components. Exposure to MHHPA may lead to work-related airway diseases such as rhinitis, conjunctivitis, and asthma. Twelve subjects employed at a plant manufacturing electrical capacitors using MHHPA were included in this study. Nasal lavages were collected from subjects before work Monday morning and after work Tuesday afternoon. The levels of MHHPA adducted to serum albumin were analyzed with a straightforward work-up method. The samples were trypsinated before being analyzed with a liquid chromatography-triple quadrupole mass spectrometer. The mass spectrometer was run using selected reaction monitoring for six adducted peptides. Also, some biomarkers of effect (albumin, total protein, eosinophil cationic protein, and tryptase) were analyzed in nasal lavages. Furthermore, the metabolite MHHP acid in urine after work on Tuesday was analyzed by gas chromatography-mass spectrometry. Symptoms from the airways and the eyes and sensitization were registered. The main result of this study is that protein adducts can be analyzed in vivo after low occupational exposures to MHHPA. The results also show a correlation between adducted peptides and albumin in nasal lavage. Furthermore, there may be a difference in the potential to induce hyperresponsiveness between adducts bound to different amino acids.

Exposure to aluminium compounds, such as fluorides in gaseous and particulate form, places people who work in potrooms at risk for respiratory symptoms. Workers in potrooms, however, also are exposed to a number of other air contaminants. In this study, we present the first report of a dose-response relationship after exposure to potassium aluminium tetrafluoride (KAlF(4)) and the influence of smoking and atopy.All workers (308) from an industrial plant that used KAlF as soldering flux were invited to participate in the study. In all, 289 workers participated and 118 employees not exposed to chemicals in their professional work served as an unexposed group.In the first step, all subjects answered a questionnaire concerning respiratory symptoms and work history, and participated in a lung function examination. In a second step, all workers who reported work-related complaints from lower respiratory airways were invited to participate in medical examination, methacholine test, screening test of respiratory allergy, and skin prick test against KAlF(4).The exposed subjects had more symptoms than the unexposed group; dry cough odds ratio (OR): 5.17 (confidence interval 1.79-15.0), stuffy nose: 2.3 (1.25-4.22), nose bleeding: 10.7 (3.26-35.3) and ocular symptoms 5.01 (1.92-13.1) except for chest tightening and wheezing, and shortness of breath. The symptoms appeared in a dose response-like manner although the ORs between high and low exposed were significant for only chest tightening and wheezing, 2.62 (1.30-5.26) and stuffy nose 2.1 (1.22-3.66). Smokers and atopics did not report more frequent work-related symptoms. Smokers were significantly less hyperreactive than non-smokers, indicating a healthy-worker effect. No one showed a positive skin prick test against KAlF(4).In spite of exposure levels of KAlF(4 )well below the new Swedish threshold limit, value frequent respiratory and ocular symptoms were reported. No evidence of IgE mediated allergy was found.

Background: Organic acid anhydrides (OAA) are used as hardeners in epoxy resin systems. They are powerful sensitizers giving frequent rhinitis and asthma in exposed workers. Incidence of symptoms is unknown. Here we present the first prospective study on the associations between OAA exposure, symptoms, and effects of confounding factors. Methods: All new employees in three plants handling OAA were followed for up to 8.5 years. Before the employment, a questionnaire reporting about symptoms of eyes and airways, smoking habits, and atopy was answered. The subjects were asked at regular medical examinations about work tasks and work-related symptoms. Serum was analysed for specific OAA antibodies. Results: Mean exposures varied between 6 and 39 μg/m3. The incidence for work-related symptoms of the eyes, nose, pharynx, and lower airways was 91, 64, 46, and 31 per 1000 years of exposure, respectively. Symptoms were found frequently, even at mean exposure level at

BACKGROUND: Organic acid anhydrides are low molecular weight industrial chemicals, able to cause rhinoconjunctivitis and asthma associated with specific IgE against hapten-carrier protein conjugate. Only a proportion of exposed workers develop IgE-associated allergy to acid anhydrides. OBJECTIVE: We determined whether genetic susceptibility, in particular, HLA Class II alleles may be a risk factor. METHODS: We undertook HLA typing in 52 cases who had confirmed specific IgE and in 73 referents matched on site, age and duration of acid anhydride exposure identified in cross-sectional studies of workers exposed to hexahydrophthalic (HHPA), methylhexahydrophthalic (MHHPA) and methyltetrahydrophthalic (MTHPA) anhydrides. RESULTS: The linked alleles DQ5 (odds ratio [OR]=4.3; 95% confidence interval [95% CI]=1.7, 11) and DR1 (OR 3.0; 95% CI 1.2, 11) were more prevalent in cases than in referents. Within DQ5, DQB1(*)0501 was particularly frequent (OR 3.0; 95% CI 1.2, 7.4). CONCLUSION: DQB1(*)05 gene confers susceptibility to develop specific IgE antibodies against HHPA, MHHPA and a non-significant trend with MTHPA. DQB1(*)0501 is protective for other low molecular chemical sensitizers (isocyanates and plicatic acid) which may indicate varying affinities for the corresponding specific class II molecules.

Hexahydrophthalic anhydride (HHPA), an industrially important chemical, is a highly allergenic compound. The aim of this work was to identify proteins in nasal lavage fluid (NLF) that form adducts with HHPA. Such bindings may induce production of specific immunoglobulin E (IgE) or affect physiological mechanisms of the proteins. NLF was obtained from HHPA-exposed volunteers, workers and exposed guinea pigs. HHPA-binding proteins were visualized with immunoblotting using a polyclonal antiserum against HHPA. The proteins were excised from sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) gels, digested with trypsin and identified by tandem mass spectrometry (MS/MS) and database searches. The antiserum was found to be specific for HHPA-bound proteins. In vivo formed HHPA-binding proteins in humans were identified as antileukoproteinase, immunoglobulin G (IgG), immunoglobulin A (IgA), serum albumin and lactoferrin. In addition, several proteins binding to HHPA were found in NLFs from guinea pigs but these could not be identified from database searches. Hypotheses for development of airways diseases by adduction of this allergenic compound to the NLF proteins in humans were established.

Background Airway diseases in hairdressers are a concern. The objective of this investigation is to evaluate the risk for three respiratory symptoms, wheeze, dry cough, and nasal blockage, in hairdressers. Methods A questionnaire on respiratory symptoms, atopy, smoking, and work history was answered by 3,957 female hairdressers and 4,905 women from the general population as referents. Incidence rates (IR) and incidence rate ratios (IRRs)for the three symptoms were estimated. Results The IRs of all three studied symptoms were higher in the hairdressers compared with the referents. Smoking modified the effects of cohort affiliationfor all threesymptoms; the combined effect from hairdressing work and smoking was less than expected. In addition, the effect of cohort affiliation for wheeze was also modified by atopy, and the effect of cohort affiliation for nasal blockage was also modified by calendar year. Conclusions Hairdressing work was associated with increased incidences of respiratory symptoms. Smoking had a negative modifying effect.

Hairdressers have an increased risk for developing airway symptoms, for example, asthma and rhinitis. Persulfates, which are oxidizing agents in bleaching powder, are considered important causal agents for these symptoms. However, the underlying mechanisms are unclear. The aim was therefore to measure proteomic changes in nasal lavage fluid from persulfate-challenged subjects to identify proteins potentially involved in the pathogenesis of bleaching powder-associated rhinitis or candidate effect biomarkers for persulfate. Also, oxidized peptides were measured to evaluate their usefulness as biomarkers for persulfate exposure or effect, for example, oxidative stress. Samples from hairdressers with and without bleaching powder-associated rhinitis were analyzed with liquid chromatography tandem mass spectrometry using selected reaction monitoring to target 246 proteins and five oxidized peptides. Pathway analysis was applied to obtain a functional overview of the proteins. Several proteins involved in biologically meaningful pathways, functions, or disorders, for example, inflammatory responses, oxidative stress, epithelium integrity, and dermatological disorders, changed after the persulfate challenge. A list with nine proteins that appeared to be affected by the persulfate challenge and should be followed up was defined. An albumin peptide containing oxidized tryptophan increased 2 h and 5 h after the challenge but not after 20 min, which indicates that such peptides may be useful as oxidative stress biomarkers.

Welding fume consists of metal fumes, e.g., manganese (Mn) and gases, e.g., ozone. Particles in the respirable dust (RD) size range dominate. Exposure to welding fume could cause short- and long-term respiratory effects. The prevalence of work-related symptoms among mild steel welders was studied, and the occupational exposure to welding fumes was quantified by repeated measurements of RD, respirable Mn, and ozone. Also the variance components were studied.A questionnaire concerning airway symptoms and occupational history was answered by 79% of a cohort of 484 welders. A group of welders (N = 108) were selected and surveyed by personal exposure measurements of RD and ozone three times during 1 year.The welders had a high frequency of work-related symptoms, e.g., stuffy nose (33%), ocular symptoms (28%), and dry cough (24%). The geometric mean exposure to RD and respirable Mn was 1.3 mg/m(3) (min-max 0.1-38.3 mg/m(3)) and 0.08 mg/m(3) (min-max0.01-2.13 mg/m(3)), respectively. More than 50% of the Mn concentrations exceeded the Swedish occupational exposure limit (OEL). Mainly, low concentrations of ozone were measured, but 2% of the samples exceeded the OEL. Of the total variance for RD, 30 and 33% can be attributed to within-worker variability and between-company variability, respectively.Welders had a high prevalence of work-related symptom from the airways and eyes. The welders' exposure to Mn was unacceptably high. To reduce the exposure further, control measures in the welding workshops are needed. Correct use of general mechanical ventilation and local exhaust ventilation can, for example, efficiently reduce the exposure.

We examined how chronic respiratory symptoms, reported in a questionnaire, and results of skin prick tests and spirometry predicted variability in peak expiratory flow (PEF) among 6-12-yr-old children (n = 1,854). After characterization with skin tests and spirometry, children were followed for 2-3 mo during the winter of 1993-1994. Peak expiratory flow was measured daily in the morning and evenings. Children with asthmatic symptoms (wheeze and/or attacks of shortness of breath with wheeze in the past 12 mo and/or ever doctor diagnosed asthma) had a greater variation in PEF than children with dry nocturnal cough as their only chronic respiratory symptom. Similarly, doctor-diagnosed asthma was associated with a greater variation in PEF, also among children with asthmatic symptoms. Peak flow variability increased with an increasing number of symptoms reported in the questionnaire. Atopy, positive skin test reactions to house dust mite and cat and lowered level (as % of predicted) in FEV1 and in MMEF were also associated with an increased variation in PEF. All the differences were observed in both diurnal and day-to-day variation in PEF. In conclusion, chronic respiratory symptoms reported in a questionnaire, spirometric lung function and skin prick test results among asthmatic children predicted variation in PEF measured during a 2-3 mo follow-up. The difference in morning PEF coefficient of variation (CV) between children with asthmatic symptoms and children with cough only was somewhat bigger in girls than in boys. The effect of atopy on morning PEF CV was somewhat bigger in young than in older children.

The aim of this study was to achieve realistic levels of two different types of aerosols commonly abundant in indoor environments in an experimental chamber intended for human exposure studies and aerosol characterization. The aerosols chosen were particles from candle lights (in particle number dominated by inorganic water soluble particles) and from ozone-terpene reactions (organic particles). The aerosol generation and characterization system consisted of a controlled air tight stainless steel 22 m(3) chamber, to which the generation set-ups were connected. No air could enter or leave the chamber except through a conditioning system by which temperature, relative humidity and air exchange rate could be controlled. Candle smoke aerosol was generated from ten candles burning in a 1.33 m(3) glass and stainless steel chamber. The aerosol was diluted by clean air from the conditioning system before entering the chamber. Terpene vapor was generated by passing pure nitrogen through a glass bottle containing limonene oil. Ozone was generated by a spark discharge using pure O-2, and was added to the ventilation air flow downstream the inlet for terpene vapors and upstream the inlet to the chamber. Both aerosols were characterized with respect to number and mass concentrations, size distribution and chemical composition. Particle number concentration in the size range 10-650 nm could be varied from

Background: Exposure to diesel exhaust causes inflammatory responses. Previous controlled exposure studies at a concentration of 300 μg/m 3 of diesel exhaust particles mainly lasted for 1 h. We prolonged the exposure period and investigated how quickly diesel exhaust can induce respiratory and systemic effects. Methods: Eighteen healthy volunteers were exposed twice to diluted diesel exhaust (PM1 ~300 μg/m 3 ) and twice to filtered air (PM1 ~2 μg/m 3 ) for 3 h, seated, in a chamber with a double-blind set-up. Immediately before and after exposure, we performed a medical examination, spirometry, rhinometry, nasal lavage and blood sampling. Nasal lavage and blood samples were collected again 20 h post-exposure. Symptom scores and peak expiratory flow (PEF) were assessed before exposure, and at 15, 75, and 135 min of exposure. Results: Self-rated throat irritation was higher during diesel exhaust than filtered air exposure. Clinical signs of irritation in the upper airways were also significantly more common after diesel exhaust exposure (odds ratio=3.2, p

The effect of welding fumes on small airways was studied in 25 male subjects who welded in aluminium (Al) and to some extent also in stainless steel (SS). Despite a low exposure to welding fumes as compared to the permissible exposure limits, excretion of Al in urine was found to be increased in all subjects (median value: 0.29 mmol/mol creatinine on Friday afternoon, as compared to an upper reference level of 0.10 mmol/mol creatinine). In addition, the welders displayed increased prevalences of work-related eye and airways (pharyngitis and non-specific bronchial hyperreactivity) symptoms, as compared to 25 matched controls. Short-term welders (or = 2.5 years) had more symptoms related to the upper airways than did long-term welders, which may indicate a selection. Spirometry, closing volume and volume of trapped gas (VTG) did not deviate. However, after methacholine inhalation, the long-term welders had a significantly steeper slope of the alveolar plateau on the single-breath nitrogen wash-out test, and a slight increase in VTG, as compared to the short-term welders and the controls. These findings may indicate a welding fume-induced increase in the reactivity of the small airways. Because Al welding was far more frequent than SS welding, an association with the former seems likely.

One hundred and forty four current and 26 former workers in a plant producing barrels for rocket guns from an epoxy resin containing methyltetrahydrophthalic anhydride (MTHPA; time weighted average air concentration up to 150 micrograms/m3) were studied. They showed higher frequencies of work related symptoms from the eyes (31 v 0%; p < 0.001), nose (53 v 9%; p < 0.001), pharynx (26 v 6%; p < 0.01), and asthma (11 v 0%; p < 0.05) than 33 controls. Also they had higher rates of positive skin prick test to a conjugate of MTHPA and human serum albumin (16 v 0%; p < 0.01), and more had specific IgE and IgG serum antibodies (18 v 0%; p < 0.01 and 12 v 0%; p < 0.05 respectively). There were statistically significant exposure-response relations between exposure and symptoms from eyes and upper airways, dry cough, positive skin prick test, and specific IgE and IgG antibodies. There was a non-significant difference in reaction to metacholine between exposed workers and non-smoking controls. In workers with and without specific IgE antibodies, differences existed in frequency of nasal secretion (54 v 23%; p < 0.05) and dry cough (38 v 12%; p < 0.05). Workers with specific IgG had more dry cough (38 v 12%; p < 0.05), but less symptoms of non-specific bronchial hyperreactivity (0 v 26%; p < 0.05). Atopic workers sneezed more than non-atopic workers (65 v 30%; p < 0.01). In a prospective study five sensitised workers who left the factory became less reactive to metacholine, and became symptom free. In 41 workers who stayed, there was no improvement, despite a 10-fold reduction in exposure. The results show the extreme sensitising properties of MTHPA.