Expression of microRNAs in leukocytes and serum of asbestosis patients.

BACKGROUND: Although asbestos use is banned in many countries, long latency of asbestos-related diseases like pleural plaques or asbestosis mean it is still a public health issue. People suffering from these diseases have a higher risk of developing mesothelioma or lung cancer, which can progress quickly and aggressively. MicroRNAs were suggested as potential biomarkers in several diseases. However, in asbestosis, blood microRNAs are less explored. Since miR-32-5p, miR-143-3p, miR-145-5p, miR-146b-5p, miR-204-5p and miR-451a are involved in fibrotic processes and in cancer, expression of these microRNAs was analyzed in leukocytes and serum of asbestosis patients. METHODS: MicroRNA expression was analyzed in leukocytes and serum of 36 patients (26 affected by pleural plaques and 10 by asbestosis) and 15 healthy controls by real-time RT-PCR. Additionally, data analyses were performed regarding disease severity based on ILO classification. RESULTS: MicroRNA miR-146b-5p was significantly down-regulated in leukocytes of patients suffering from pleural plaques with a large effect indicated by η2p = 0.150 and Cohen's f = 0.42, a value of difference of 0.725 and a 95% confidence interval of 0.070-1.381. In patients suffering from asbestosis miR-146b-5p was not significantly regulated. However, data analyses considering disease severity only, revealed that miR-146b-5p was significantly down-regulated in leukocytes of mildly diseased patients compared to controls with a large effect indicated by η2p = 0.178 and Cohen's f = 0.465, a value of difference of 0.848 and a 95% confidence interval of 0.097-1.599. Receiver operating characteristic (ROC) curve and an area under the ROC curve value of 0.757 for miR-146b-5p indicated acceptable discrimination ability between patients suffering from pleural plaques and healthy controls. Less microRNAs were detectable in serum than in leukocytes, showing no significant expression differences in all participants of this study. Moreover, miR-145-5p was regulated significantly differently in leukocytes and serum. An R2 value of 0.004 for miR-145-5p indicated no correlation in microRNA expression between leukocytes and serum. CONCLUSION: Leukocytes seem more suitable than serum for microRNA analyses regarding disease and potentially cancer risk assessment of patients suffering from asbestos-related pleural plaques or asbestosis. Long-term studies may reveal whether down-regulation of miR-146b-5p in leukocytes might be an early indicator for an increased cancer risk.

Assessing Energy Expenditure in Female Healthcare Workers in a University Hospital.

INTRODUCTION: The assessment of energy expenditure (EE) at workplaces maintains a central topic in occupational health due to increasing work-related issues. Today 80% of employees in the healthcare system are women. Limited research concerning their physical activity at work is available. The purpose of the study was the investigation of body composition, maximum physical capacity and quantification of physical work activity for female healthcare workers under real-time conditions. METHODS: Occupational physical activity (PA) of 33 female healthcare workers in a university hospital was quantified. Health associate professionals (HAP), health professionals (HP), and females working from cleaners and helpers (CH) department participated. All underwent cardio pulmonary exercise test. For every working task VO2, VCO2 and RER were measured and EE was calculated individually for each task. RESULTS: Forty-two different working tasks were identified and grouped in seven categories to compare physical activity (PA): 'office and laboratory work', 'bedside patient care', 'instrument reprocessing, packing boxes', 'walking with patient, or alone', 'pushing carts or wheelchairs', 'strenuous cleaning in bent posture' and 'lifting heavy boxes, weights or items'. By comparing groups of healthcare workers, CH and HAP spent significant (p < 0.01) more EE (in kcal/min) 3.9 resp. 3.2 than HP 2.5. Light PA e.g. office and laboratory work (2.7 ± 0.6) and bedside patient care (2.9 ± 0.7) were accomplished by HP and HAP while HAP and CH performed moderate PA such as 'packing boxes' (3.6 ± 0.8), 'pushing carts' and 'strenuous cleaning' (4.7 ± 0.9). Work performed by CH and HAP, i.e. 'strenuous cleaning' and 'lifting heavy items' showed highest kcal per kg Fat Free Mass (FFM) per hour with 5.80 [4.05-7.81] and 6.94 [5.18-9.03] kcal/kgFFM/h. CONCLUSION: Our findings lend preliminary support to the hypothesis that the majority of activities in female healthcare workers were of low and moderate PA and can be accomplished by middle aged and even older female workers. CH performed tasks with heavy physical activities (PA) like cleaning and lifting heavy weights. HAP performed light/moderate PA below their maximum physical capacity.

Rounded atelectasis after exposure to refractory ceramic fibres (RCF).

BACKGROUND: Refractory Ceramic fibres (RCF) are man-made mineral fibres used in high performance thermal insulation applications. Analogous to asbestos fibres, RCF are respirable, show a pleural drift and can persist in human lung tissue for more than 20 years after exposure. Pleural changes such as localised or diffuse pleural thickening as well as pleural calcification were reported. RESULT: A 45 years old man worked in high performance thermal insulation applications using refractory ceramic fibres (RCF) for almost 20 years. During a occupational medical prophylaxis to ensure early diagnosis of disorders caused by inhalation of aluminium silicate fibres with X-ray including high-resolution computed tomography (HRCT), bilateral pleural thickening was shown and a pleural calcification next to a rounded atelectasis was detected. Asbestos exposure could be excluded. In pulmonary function test a restrictive lung pattern could be revealed. In work samples scanning electron microscopy (SEM) including energy dispersive X-ray analysis (EDX) classified used fibres as aluminium silicate fibres. X-ray powder diffraction (XRD) and transmission electron microscopy (TEM) showed crystalline as well as amorphous fibres. CONCLUSIONS: A comprehensive lung function analysis and in case of restrictive lung disorders additional CT scans are needed in RCF exposed workers in accordance to the guidelines for medical occupational examinations comparable to asbestos exposed workers.

Physical effort of middle-aged women in a university hospital - Field tests in comparison to standardized cardiopulmonary exercise testing (CPET).

Physical effort of workload of female employees in the healthcare system is perceived to rise. Research focused mainly on physical activity levels of registered nurses (RN). Therefore, we investigated physical strain during daily routine of other hospital workers next to RN. O2uptake, heart rate, breathing frequency and ventilation were measured in 33 female medical (associate) professionals (MAP) and Cleaners&Helpers (Cl&H) using Oxycon Mobile. Physical work load was compared to standardized CPET. Wilcoxon-test and ANOVA were calculated using SPSS 20.0. Cl&H performed heavy-lifting and had the lowest power during CPET. The O2-uptake for heavy-lifting as strong effort, differed significantly from office work (p < 0.001) and bedside-patient-care (p = 0.001). Compared with metabolic equivalent (MET) cleaning, heavy-lifting, and office work are underestimated. Bedside-patient-care, walking, pushing performed by MAP are overestimated. While Cl&H had the lowest maximal power in CPET, their work required the highest O2-uptake. The tasks are underestimated in the MET-tables.

High rate biological contactor system using waste activated sludge from trickling filter/solids contact process.

A high-rate biological contactor process (HRBC) can be used as primary treatment instead of a clarifier to remove particulate, colloidal and soluble fractions of organic matter via biosorption plus flotation and divert it to anaerobic digestion for methane production, simultaneously reducing secondary aeration energy demand. Pilot and bench tests were conducted at a range of contact times (15-60 min) and contactor dissolved oxygen (DO) (0.2-2.0 mg/L) using waste activated sludge (WAS) from a trickling filter/solids contact (TF/SC) process in the HRBC. Biosorption performance was lowest when contact times were <30 min and unstable at DO < 0.5 mg/L. The overall average of 20% sCOD capture was similar to previous findings by others using WAS from conventional AS. The biomethane potential (BMP) of the HRBC float material can be as high as that of primary sludge (340-400 mL CH4/g VS), which is much greater than WAS. Operating the HRBC with a long contact time (>30 min) or with high DO (>1 mg/L) increases the amount of biosorption but reduces the BMP of the float. It was also found that biosorption only effectively occurs when a WAS is paired with the wastewater from the same facility.

Comparative proteomic analysis in serum of former uranium miners with and without radon induced squamous lung cancer.

SUMMARY: Former uranium miners of the Wismut Company, East Germany, have been exposed to ionizing radiation from radon decay products and therefore were at high risk for lung cancer. Since histological types of cancer in the so called Wismut cohort revealed an association of high radon exposure with a higher relative frequency of squamous cell carcinoma (SqCC), we used comparative proteomic analysis to identify differentially expressed proteins in serum exposed uranium miners with SqCC. METHODE: Pooled sera of exposed former uranium miners without lung disease and pooled sera of former uranium miners with SqCC were analysed by 2-D gel electrophoresis. MALDI-TOF-MS was performed from reproducable, significantly, at least 5-fold up-regulated protein spots. Proteins were identified by MASCOT peptide mass fingerprint search. Additionally a receiver operating characteristic curve for CYFRA 21-1 was created. RESULTS: The protein spots were identified as Keratin 10 (K10), Keratin 1 (K1), complement factor H (CFH) and a haptoglobin (Hpt) fragment. The sensitivity for CYFRA 21-1 reveals 60% at a specifity of 95 and 80% at a specifity of 80%. Plotting the sensitivity against specifity reveals an AUC of 0.88. CONCLUSION: In SqCC Keratin 10 and 1 were strongly induced. This was associated with CYFRA 21-1, confirming the cytokeratin fragment as a tumormarker.

Comparative Assessment of CPET Versus Typical Work-related Activities in Women With and Without Mild COPD.

BACKGROUND: Prevalence of chronic obstructive pulmonary disease (COPD) is increasing in Germany. This study examined the work performance of healthy women compared to those with mild COPD. PATIENTS AND METHODS: Nineteen women suffering from COPD Global Initiative for Chronic Obstructive Lung Diseases stage I and 41 healthy women underwent standardised cardiopulmonary exercise test (CPET) in comparison to 5 typical work-related tasks. Oxygen uptake, carbon dioxide output, ventilation volume, breathing frequency, heart rate and respiratory exchange ratio (RER) were measured. The activities were quantified. Wilcoxon test and ANOVA were calculated using the SPSS software. RESULTS: Patients with COPD had a lower exercise capacity compared to healthy women and also showed lower performance during work-related activities. Patients with COPD had a lower oxygen uptake (p<0.001), a higher breathing frequency was accompanied by a higher Borg scale. The heart rate and the ventilation volume as a percentage of maximum CPET were significantly higher in patients with COPD. Women suffering from progressive symptoms had lower oxygen uptakes and RER, whilst breathing frequency and Borg scale were elevated. CONCLUSION: Even at an early stage of the disease, patients with COPD exhibited limitations in work-related tasks.

Oxidative and cytotoxic stress induced by inorganic granular and fibrous particles.

The hazards of granular and fibrous particles have been associated with the generation of reactive oxygen species (ROS), which in turn is often associated with physicochemical properties exhibited by these particles. In the present study, the ability of various types of fibrous and granular dusts to generate oxidative stress, and their cytotoxicity, was investigated. Biopersistent granular dusts employed in the present study included micro­ and nanosized titanium dioxide with rutile or anatase crystal structure modifications. Additionally, glass fibres, chrysotile and crocidolite asbestos representative of fibrous dust were selected. Detailed characterisation of particles was performed using scanning electron microscopy, and the effect of exposure to these particles on cell viability and intracellular ROS generation was assessed by PrestoBlue and 2',7'­dichlorofluorescein assays, respectively. A549 human lung epithelial adenocarcinoma cells were exposed to increasing concentrations (0.1­10 µg/cm2) of particles and fibres for 24 h. Subsequently, the gene expression of X­linked inhibitor of apoptosis (XIAP), superoxide dismutase (SOD)1 and SOD2 were analysed by reverse transcription­quantitative polymerase chain reaction. All investigated granular particles induce ROS production in A549 lung carcinoma cells within 24 h. Hematite increased ROS production in a dose­dependent manner. A concentration of >1 µg/cm2 TiO2 na with its disordered surface, demonstrated the greatest ability to generate ROS. Therefore, the crystalline surface structure of the particle may be considered as a determinant of the extent of ROS induction by the particle. Fibrous particle compared with granular particles were associated with a lower ability to generate ROS. Glass fibres did not significantly increase ROS production in A549 cells, but elevated gene expression of SOD2 was observed. The results demonstrated that in general, the ability of particles to generate ROS depends on their number and crystal phase. Therefore, the present study helps to understand the cause of particle toxicity.

Noise exposure and auditory thresholds of military musicians: a follow up study.

BACKGROUND: Military musicians are working in a noisy environment with high sound exposure levels above the international standards. Aim of the current study is to find out, whether they develop the expected hearing impairments. Adherence to the regulations for prevention in musicians is more difficult than in other occupational fields. METHODS: In an interval of 13.3 years, 36 out of 58 male military musicians of a German army music corps were subjected twice to an audiometric audit. There were no exclusion criteria apart from acute ENT infections (three musicians). These results were compared with one another and evaluated by means of statistical methods for relationships with several factors. RESULTS: At frequencies below 3 kHz, the follow-up audiograms were up to 5 dB better than the preliminary examination. From 4 kHz up to 8 kHz the preliminary investigations showed less hearing impairment. Averaging all frequencies the improvement of hearing ability was around 1 dB. Above 1 kHz the average hearing of the right ear was up to 7 dB better than that of the left ear. Age-induced hearing loss was 3 to 8 dB lower than predicted by ISO standards over the entire frequency range. The side of the ear (right/left) and the frequency (3, 4, and 6 kHz) were significant (p < 0.05) in hearing loss, whereas the influence of the instrument and the acoustic traumata were not. CONCLUSION: Despite the high noise levels, the average hearing ability of the 36 military musicians during the investigation period only slightly deteriorated in the noise-sensitive frequencies (3, 5 and 6 kHz). Music may be less harmful than industrial noise, or the long-term auditory training of the musicians leads to a delayed presbycusis.

Impact of biopersistent fibrous dusts on glycolysis, glutaminolysis and serine metabolism in A549 cells.

The conversion rates of different metabolic pathways summarized as a metabolic signature mirror the physiological functions and the general physiological status of a cell. The present study compared the impact of crocidolite and chrysotile asbestos, glass fibers and multi­walled carbon nanotubes (MWCN) of two different lengths (1­2 µm and 5­15 µm) on the conversion rates in glycolysis, glutaminolysis and serine metabolism of A549 cells. The concentration tested was 1 µg/cm2 for all fibers. A concentration of 5 µg/cm2 was additionally used for chrysotile and crocidolite, and 25 µg/cm2 for glass fibers and MWCN. With respect to the inhibitory effect on cell proliferation and the extent of metabolic alterations, the present study revealed the following ranking among the fibers tested: Chrysotile>crocidolite>glass fibers>MWCN 5­15 µm>MWCN 1­2 µm. For the asbestos and glass fibers this ranking correlated best with the number of fibers. It appeared that the results observed for MWCN did not match this correlation. However, electron microscopy revealed an agglomeration of MWCN. The agglomeration decreased the toxicologically relevant number of fibers by forming larger particle­like shapes and explained the smaller effects of MWCN 5­15 µm and 1­2 µm on cell proliferation and metabolism.

Noise exposure and auditory thresholds of German airline pilots: a cross-sectional study.

OBJECTIVE: The cockpit workplace of airline pilots is a noisy environment. This study examines the hearing thresholds of pilots with respect to ambient noise and communication sound. METHODS: The hearing of 487 German pilots was analysed by audiometry in the frequency range of 125 Hz-16 kHz in varying age groups. Cockpit noise (free-field) data and communication sound (acoustic manikin) measurements were evaluated. RESULTS: The ambient noise levels in cockpits were found to be between 74 and 80 dB(A), and the sound pressure levels under the headset were found to be between 84 and 88 dB(A).The left-right threshold differences at 3, 4 and 6 kHz show evidence of impaired hearing at the left ear, which worsens by age.In the age groups <40/≥40 years the mean differences at 3 kHz are 2/3 dB, at 4 kHz 2/4 dB and at 6 kHz 1/6 dB.In the pilot group which used mostly the left ear for communication tasks (43 of 45 are in the older age group) the mean difference at 3 kHz is 6 dB, at 4 kHz 7 dB and at 6 kHz 10 dB. The pilots who used the headset only at the right ear also show worse hearing at the left ear of 2 dB at 3 kHz, 3 dB at 4 kHz and at 6 kHz. The frequency-corrected exposure levels under the headset are 7-11 dB(A) higher than the ambient noise with an averaged signal-to-noise ratio for communication of about 10 dB(A). CONCLUSIONS: The left ear seems to be more susceptible to hearing loss than the right ear. Active noise reduction systems allow for a reduced sound level for the communication signal below the upper exposure action value of 85 dB(A) and allow for a more relaxed working environment for pilots.

How conflicted authors undermine the World Health Organization (WHO) campaign to stop all use of asbestos: spotlight on studies showing that chrysotile is carcinogenic and facilitates other non-cancer asbestos-related diseases.

The silicate mineral asbestos is categorized into two main groups based on fiber structure: serpentine asbestos (chrysotile) and amphibole asbestos (crocidolite, amosite, anthophyllite, tremolite, and actinolite). Chrysotile is used in more than 2 000 applications and is especially prevalent in the construction industry. Although its use is banned or restricted in more than 52 countries, an estimated 107 000 workers die from asbestos exposure each year, and approximately 125 million workers continue to be exposed. Furthermore, ambient exposures persist to which the public is exposed, globally. Today, the primary controversies regarding the use of asbestos are the potencies of different types of asbestos, as opposed whether or not asbestos causes morbidity and mortality. The asbestos industry has promoted and funded research based on selected literature, ignoring both clinical and scientific knowledge. In this piece, we highlight a prominent example of a conflicted publication that sought to undermine the World Health Organization (WHO) campaign to stop the use of all forms of asbestos, including chrysotile asbestos. Independent and rigorous scientific data provide sufficient evidence that chrysotile asbestos, like other forms of asbestos, is a cause of asbestos-related morbidity and premature mortality.

Pulmonary fibrosis following household exposure to asbestos dust?

An 81-year-old woman was dying from histologically confirmed pulmonary fibrosis without having had any asbestos exposure in the workplace. The lung dust fibre analysis showed significantly increased "asbestos bodies" (AB) (2,640 AB per gram of wet lung tissue) and asbestos fibre concentrations (8,600,000 amphibole fibres of all lengths and 540,000 amphibole fibres with a length ≥5 µm per gram of dry lung tissue). Asbestos exposure was revealed to have occurred during household contact after 27 years of washing her husband's industrial clothing that had been contaminated by asbestos at his workplace in an asbestos textile factory. Household asbestos dust exposure as a risk or co-factor in the aetiology of the fatal pulmonary fibrosis is discussed.

CYP1B1 mRNA inducibility due to benzo(a)pyrene is modified by the CYP1B1 L432V gene polymorphism.

Benzo(a)pyrene (BaP), a primary component of tobacco smoke, is activated by cytochrome P450 1B1 (CYP1B1). Smokers homozygous for the C-allele (*1/*1) at the CYP1B1 Leu432Val polymorphism have shown increased CYP1B1 expression, compared to smokers homozygous for the G-allele *3/*3. Since no difference has been shown in CYP1B1 expression between both genotypes in non-smokers, we assumed that the genetic impact is produced in combination with an exogenous induction (e.g. BaP). To confirm this theory and to quantify the effect, we induced human leucocytes with increasing BaP concentrations and determined CYP1B1 mRNA expression with real-time polymerase chain reaction (PCR). We incubated human leucocytes from 27 healthy donors with BaP concentrations ranging from 2.5 to 250 µM. We identified the CYP1B1 genotypes by melting curve analysis and assessed relative CYP1B1 mRNA expression using real-time PCR. Expression was related to ß-2-microglobulin with the 2(-ΔΔCT) method. Inducibility of CYP1B1 mRNA by BaP was higher in leucocytes carrying the CYP1B1*1/*1 genotype than in leucocytes carrying the CYP1B1*3/*3 genotype (P = 0.012). We revealed significant differences, with BaP concentrations of 2.5 µM (P = 0.0094), 5 µM (P = 0.027), 10 µM (P = 0.0006), 25 µM (P = 0.0007) and 50 µM (P = 0.017). Homozygous carriers of the C-allele (*1/*1) at the CYP1B1 Leu432Val polymorphism show a higher response to environmental factors, such as carcinogenic BaP, than homozygous carriers of the G-allele *3/*3.

Interleukin-6 contributes to the paracrine effects of cardiospheres cultured from human, murine and rat hearts.

Cardiosphere-derived cells (CDCs) were cultured from human, murine, and rat hearts. Diluted supernatant (conditioned-medium) of the cultures improved the contractile behavior of isolated rat cardiomyocytes (CMCs). This effect is mediated by the paracrine release of cytokines. The present study tested the hypothesis, that the cardiovascular state of the donor's heart influences this effect on CMCs and tries to identify the responsible factors. CDCs were cultured from human tissue samples of cardiac surgery and from murine and rat hearts. The supernatants of cultured CDCs from hypertensive humans and rats showed a higher improvement of the contractile behavior of CMCs compared to CDCs of normotensive origin. Subsequently, the cytokine profile of the supernatants was analyzed. Among the cytokines elevated in supernatants originating from hypertensive humans or rats was Interleukin-6. CDCs were also generated from Interleukin-6(-/-) -mice and their wildtype littermates. The supernatant of the cultured Interleukin-6(-/-) -CDCs had no effect on the contractile behavior, whereas the supernatant of the Interleukin-6(+/+) -CDCs showed a positive effect. To confirm the hypothesis that Interleukin-6 contributes to the paracrine effects, CMCs were incubated with Interleukin-6. It improved the contractile function in a concentration dependent way. Finally, the effect of the supernatant of cultured CDCs derived from a hypertensive human sample could be abolished by simultaneous incubation with a specific Interleukin-6 antibody. CDCs release cytokines that improve the contractile behavior of CMCs. This effect is more intense in CDCs from hypertensive donors. Interleukin-6 is involved in this phenomenon.

Age-dependent improvement of hearing ability in children: an international approach.

OBJECTIVES: Pure-tone auditory thresholds in children are below the standardized hearing threshold levels described by ). The development of hearing ability in Chinese and German children at different ages is analyzed and compared with data in the literature. Extended high frequencies above 8 kHz are included due to their vulnerability to noise. DESIGN: Ninety-one children in China and 197 children at a typical primary school in Germany underwent audiometric tests at 17 frequencies ranging from 125 Hz to 16 kHz. To analyze effects of age the children were assessed in age groups of 6 to 9, 9 to 12, and 13 to 16 years of age. RESULTS: Children in China and Germany have the poorest hearing sensitivity at low frequencies (below 1 kHz) and the best sensitivity at the extended high frequencies above 8 kHz. The mean deviations (both ears) from the standard thresholds for adults 18 to 25 years of age, averaged over all frequencies, are 6.7 dB for Chinese and 7.1 dB for German children in the youngest age groups. In the Chinese age group of 9- to 12-year olds the averaged threshold is 4.5 dB and for the same German age group 3.6 dB. For the Chinese age group of 13- to 16-year olds the averaged threshold is 3.3 dB. The improvements of the older German age group compared with the younger are significant at p < 0.05 and are nearly twice as high compared with the comparable Chinese age groups. CONCLUSIONS: Age-dependent improvements of hearing ability are evident in children and should be considered in evaluating audiometric test results. Audiometric tests in the extended high-frequency range could be used as an early warning system for future degeneration of hearing ability.

Induction of altered mRNA expression profiles caused by fibrous and granular dust.

Natural and synthetic fibres and particles are being introduced into the workplace and environment daily. Comparative analyses of the induced signalling pathways are essential in order to understand the potential hazards of these particles. To identify the molecular characteristics of particles and fibres, we selected crocidolite and chrysotile asbestos as representatives for fibered dust and titanium dioxide (TiO2) (100-200 nm), zirconium dioxide (ZrO2) (50-100 nm) and hematite (Fe2O3) (20 nm) as representatives for bio-persistent granular dust. SV-40 virus-transformed human bronchial epithelial cells (BEAS-2B) were exposed to well-defined fibres and particles. RT2 Profiler™ PCR Array Human Stress & Toxicity PathwayFinder was used to compare the relative mRNA expression of 84 genes. A detailed characterization of the dust samples used in this study was accomplished to ensure comparability to other studies. Investigation of mRNA expression of 84 signalling molecules attributed to pathways such as DNA damage and repair; oxidative/metabolic stress; growth arrest and senescence; inflammation, proliferation and carcinogenesis; and heat shock and apoptosis revealed that crocidolite and chrysotile asbestos induced mRNA expression of pathway molecules involved in proliferation and carcinogenesis, as well as inflammation. Titanium dioxide, zirconium dioxide and hematite mainly induced pathway molecules responsible for oxidative/metabolic stress and inflammation. Our findings suggest that the hazards of fibered dust mainly include the induction of direct toxicity by altering signalling pathways such as carcinogenesis and proliferation, while granular dust shows indirect toxicity by altering signalling pathways involved in inflammatory processes. PCR arrays, therefore, may be a helpful tool to estimate the hazard risk of new materials.

Spiroergometric parameters at maximal exercise testing assessed functional respiratory impairment in asbestos-induced fibrosis.

INTRODUCTION: Exercise intolerance is typical for asbestosis. We examined the correlation of spiroergometric parameters with severity of asbestosis according to the International Labour Office (ILO) classification. Patients were compared to a healthy control group. OBJECTIVES: Nineteen consecutive male patients with compensated asbestosis and 24 healthy subjects were examined. METHODS: All participants underwent pulmonary functional testing including maximal cardiopulmonary exercise testing (CPET). Results were compared to those of healthy subjects; the correlation to disease status was investigated. RESULTS: Significantly lower VCin , FVC, FEV1 , MEF50 , TLC and PaO2 at rest (P<0.001) were observed in asbestosis patients. Lower peak (weight-related) work rate (WR, WR/kg), (weight-related) oxygen uptake (V'O2 , V'O2 /kg), oxygen pulse (V'O2 /hr), ventilation volume (V'E ), carbon dioxide output (V'CO2 ) and blood lactate was associated (P<0.001) with more severe asbestosis according to the ILO-classification. Significant positive correlations (P<0.001) were seen for alveolar-arterial oxygen difference [P(A-a)O2 ] and PaCO2 . Multiple regression analysis revealed that asbestosis was the only significant factor associated with the spiroergometric parameters (P<0.001). A reduction of V'O2 , V'O2 /kg, V'O2 /hr, V'E , or V'CO2 at identical submaximal workload could neither be detected among the asbestosis severity nor in comparison to healthy subjects. Only the respiratory frequency was depending on severity of asbestosis. CONCLUSIONS: The severity of asbestosis correlates with maximal WR, V'O2 , V'O2 /hr, V'E and gas exchange. At identical workload the discrimination between patients and controls was only possible concerning the respiratory frequency. For detection of limitations in asbestosis patients, maximal CPET is recommended.

Submaximal spiroergometric parameters are unaffected by severity of chronic obstructive pulmonary diseases.

BACKGROUND/AIM: The Global initiative for chronic obstructive lung diseases (GOLD) reports a staging system for chronic obstructive pulmonary disease (COPD) based on airflow limitations at rest. Cardiopulmonary exercise testing (CPET) is used in surveys to determine the remaining working capacity concerning the degree of disability and the disability benefit payment after rehabilitation in patients with COPD. The aim of the present study was to examine if sub-maximal exercise levels also correlate with COPD disease stage. PATIENTS AND METHODS: A total of 63 consecutive male patients with COPD and 24 elderly healthy volunteers underwent pulmonary functional tests including CPET. Work capacity, oxygen uptake, ventilation volume, carbon dioxide production and arterial blood gases were measured. RESULTS: Exercise capacity, oxygen uptake, ventilation volume, oxygen pulse, carbon dioxide output and arterial oxygen pressure decreased significantly (p<0.001) with advancing GOLD stage. Significant positive correlations (p<0.001) to GOLD stage were seen for the alveolar-arterial differences for oxygen pressure and arterial carbon dioxide pressure. Weight-related exercise capacity (p<0.001), oxygen uptake (p<0.01) and lactate concentrations (p<0.05) were significantly lower in patients with COPD. Reduction of (weight-related) oxygen uptake, ventilation volume, oxygen pulse or carbon dioxide output at identical sub-maximal workload was not detected according to GOLD stage, not in comparison of patients with healthy individuals. CONCLUSION: The GOLD staging system correlates with maximal CPET. At identical workload, discrimination between patients with different GOLD stages and healthy individuals was not possible. For the detection of exercise impairment, maximal CPET is recommended.

Combination of mesothelin and CEA significantly improves the differentiation between malignant pleural mesothelioma, benign asbestos disease, and lung cancer.

INTRODUCTION: Soluble mesothelin-related peptides (SMRP) have been reported as potential markers for the diagnosis of malignant pleural mesothelioma (MPM). We wondered, whether a combination with a carcinoembryonic antigen (CEA) test might improve the relatively low diagnostic yield of the SMRP test. METHODS: In a retrospective study, SMRP (mesothelin) and CEA serum concentrations were measured, using commercially available kits, in 93 previously untreated MPM patients, 75 patients with benign asbestos disease, and 139 patients suffering from lung cancer (LC). RESULTS: The differentiation between MPM, LC, and benign asbestos disease could be improved by applying the ratio mesothelin/CEA. Whereas CEA expression was found to be low in MPM, most LC patients had elevated CEA serum levels. The area under curve (AUC) of the receiver operator characteristics curve for mesothelin alone was found to be only 0.708. For mesothelin/CEA the AUC of the receiver operator characteristics curve increased to 0.978. The sensitivity was 93% (69%) at 95% (100%) specificity for the differentiation between MPM and LC. Comparison of MPM and benign asbestos disease showed that the AUC was 0.887 and the sensitivity 56% (47%) at 95% (100%) specificity. In contrast, the AUC for the mesothelin test alone was only 0.715, and for the CEA test alone it was 0.16. An average increment in sensitivity of 38% (range, 16%-63%) could be achieved by the quotient mesothelin/CEA compared with the sensitivity of mesothelin alone. CONCLUSION: The diagnostic yield of the mesothelin test can be considerably improved when combined with a CEA test with regard to the differential diagnosis between MPM and LC and between MPM and benign asbestos disease.