Benign Asbestos-related Diseases Research Articles

Lung cancer and mesothelioma risks in a prospective cohort of workers with asbestos-related lung or pleural diseases.

Asbestos causes mesothelioma and lung cancer. In the European Union, asbestos was banned in 2005, but it is still in use in many other countries. The aim of this study was to estimate the lung cancer and mesothelioma incidence risk of men with benign asbestos-related lung or pleural diseases. Between 2008 and 2018, 2439 male participants of a German surveillance program for asbestos workers were included in the cohort. All participants had a recognized occupational asbestos-related disease of the pleura or lung. We estimated the mesothelioma and lung cancer risks by calculating standardized incidence ratios (SIR) with corresponding 95% confidence intervals (95% CI). We observed 64 incident lung cancer and 40 mesothelioma cases in the cohort. An SIR of 17.60 (95% CI: 12.57-23.96) was estimated for mesothelioma and 1.27 (95% CI: 0.98-1.62) for lung cancer. The presence of pleural plaques was associated with a strongly increased risk (SIR: 13.14; 95% CI: 8.51-19.40) for mesothelioma, but not for lung cancer (SIR: 1.05; 95% CI: 0.76-1.41). The highest lung-cancer risk (SIR: 2.56; 95% CI 1.10-5.04) was revealed for cohort members with less than 40 years since first asbestos exposure. Lung cancer risks by duration of asbestos exposure did not show a consistent time trend, but for time since last exposure a trend for mesothelioma was seen. Compared to the general population, we demonstrated an association between benign asbestos-related lung or pleural disease and mesothelioma risk in workers with a history of occupational asbestos exposure. Because lung-cancer risk is dominated by smoking habits, a possible effect of asbestos exposure may have been masked. Efforts should be made to ban production and use of asbestos worldwide and to establish safe handling rules of legacy asbestos.

Follow-up of Soluble Mesothelin-Related Protein Levels in Participants With Asbestos-Related Disorders

BackgroundAsbestos exposure is associated with the development of the cancer malignant mesothelioma (MM). Measurement of soluble mesothelin-related protein (SMRP) has been suggested as a method for detection of MM in its early stages. We prospectively examined SMRP levels in participants with asbestos exposure who are a group at a high risk of development of MM.MethodsThis study was a follow-up of our cohort of 322 asbestos-exposed participants. No further participants developed MM or malignancy over the study period. Mean follow-up time was 22.9 months.ResultsMean (standard deviation) SMRP levels at baseline and follow-up were 0.94 (0.79) and 0.91 (0.86) nmol/L (p = 0.1033), respectively. Mean SMRP levels of the healthy individuals exposed to asbestos at baseline was significantly lower than those of participants with asbestosis and pleural plaques alone; similar patterns were found on follow-up measurements. There was a statistically significant effect of age on serial SMRP measurements. Our study confirms higher levels in participants with nonmalignant asbestos-related disorders. Levels decreased in asbestos-related disorders other than asbestosis, where a small increase was observed. We did not detect any further cases of malignancy.ConclusionMonitoring programs for early detection of MM need to take into account increased SMRP levels found in benign asbestos-related diseases.

Prediagnostic detection of mesothelioma by circulating calretinin and mesothelin \u2013 a case-control comparison nested into a prospective cohort of asbestos-exposed workers

Malignant mesothelioma (MM) is strongly associated with a previous asbestos exposure. To improve timely detection of MM in asbestos workers, better screening tools – like minimally-invasive biomarkers – are desirable. Between 2008 and 2018 2,769 patients with benign asbestos-related diseases were recruited to participate in annual screens. Using a nested case-control design the protein markers calretinin and mesothelin were determined by enzyme-linked immunosorbent assays in prediagnostic plasma samples of 34 MM cases as well as 136 matched controls from the cohort. Conditional on a pre-defined specificity of 98% for calretinin and 99% for mesothelin the markers reached individual sensitivities of 31% and 23%, respectively, when including the incident cases with samples taken between one and 15 months before diagnosis. The combination of both markers increased the sensitivity to 46% at 98% specificity. Marker complementation increased with earlier sampling. The marker combination improves the sensitivity of the individual markers, indicating a useful complementation and suggesting that additional markers may further improve the performance. This is the first prospective cohort study to evaluate a detection of MM by calretinin and its combination with mesothelin up to about a year before clinical diagnosis. Whether an earlier diagnosis will result in reduced mortality has yet to be demonstrated.

Exhaled breath to screen for malignant pleural mesothelioma: a validation study.

Malignant pleural mesothelioma (MPM) is predominantly caused by asbestos exposure and has a poor prognosis. Breath contains volatile organic compounds (VOCs) and can be explored as an early detection tool. Previously, we used multicapillary column/ion mobility spectrometry (MCC/IMS) to discriminate between patients with MPM and asymptomatic high-risk persons with a high rate of accuracy. Here, we aim to validate these findings in different control groups.Breath and background samples were obtained from 52 patients with MPM, 52 healthy controls without asbestos exposure (HC), 59 asymptomatic former asbestos workers (AEx), 41 patients with benign asbestos-related diseases (ARD), 70 patients with benign non-asbestos-related lung diseases (BLD) and 56 patients with lung cancer (LC).After background correction, logistic lasso regression and receiver operating characteristic (ROC) analysis, the MPM group was discriminated from the HC, AEx, ARD, BLD and LC groups with 65%, 88%, 82%, 80% and 72% accuracy, respectively. Combining AEx and ARD patients resulted in 94% sensitivity and 96% negative predictive value (NPV). The most important VOCs selected were P1, P3, P7, P9, P21 and P26.We discriminated MPM patients from at-risk subjects with great accuracy. The high sensitivity and NPV allow breath analysis to be used as a screening tool for ruling out MPM.

Breath analysis by gas chromatography-mass spectrometry and electronic nose to screen for pleural mesothelioma: a cross-sectional case-control study.

RationaleMalignant pleural mesothelioma (MPM) is mainly caused by previous exposure to asbestos fibers and has a poor prognosis. Due to a long latency period between exposure and diagnosis, MPM incidence is expected to peak between 2020-2025. Screening of asbestos-exposed individuals is believed to improve early detection and hence, MPM management. Recent developments focus on breath analysis for screening since breath contains volatile organic compounds (VOCs) which reflect the cell’s metabolism.ObjectivesThe goal of this cross-sectional, case-control study is to identify VOCs in exhaled breath of MPM patients with gas chromatography-mass spectrometry (GC-MS) and to assess breath analysis to screen for MPM using an electronic nose (eNose).MethodsBreath and background samples were taken from 64 subjects: 16 healthy controls (HC), 19 asymptomatic former asbestos-exposed (AEx) individuals, 15 patients with benign asbestos-related diseases (ARD) and 14 MPM patients. Samples were analyzed with both GC-MS and eNose.ResultsUsing GC-MS, AEx individuals were discriminated from MPM patients with 97% accuracy, with diethyl ether, limonene, nonanal, methylcyclopentane and cyclohexane as important VOCs. This was validated by eNose analysis. MPM patients were discriminated from AEx+ARD participants by GC-MS and eNose with 94% and 74% accuracy, respectively. The sensitivity, specificity, positive and negative predictive values were 100%, 91%, 82%, 100% for GC-MS and 82%, 55%, 82%, 55% for eNose, respectively.ConclusionThis study shows accurate discrimination of patients with MPM from asymptomatic asbestos-exposed persons at risk by GC-MS and eNose analysis of exhaled VOCs and provides proof-of-principle of breath analysis for MPM screening.

OA22.05 Breath Analysis by Gas Chromatography-Mass Spectrometry Can Be Used to Screen for Pleural Mesothelioma

Malignant pleural mesothelioma (MPM) is an asbestos-related tumor with poor prognosis. Since MPM is diagnosed at advanced stage due to non-specific symptoms and investigations, it is thought that only an early diagnosis will improve patient’s outcome. Breathomics allows to detect volatile organic compounds (VOCs) in breath which can be used as non-invasive biomarkers. Although we were able to discriminate MPM patients from controls using ion mobility spectrometry breathomics, we were not able to identify specific VOCs. Therefore, we aimed to identify VOCs in the breath of MPM persons and persons at risk with gas chromatography-mass spectrometry (GC-MS). Fourteen MPM patients, eighteen asymptomatic asbestos-exposed individuals, 16 individuals with benign asbestos-related diseases and fourteen healthy non-exposed persons were included. After 2 hours of fasting, participants breathed tidally for 5 minutes through a mouthpiece connected to a VOC filter. Subsequently, a full vital capacity was captured in a Tedlar bag of which 500 ml was immediately transferred on a TenaxGR-column. Samples were thermally desorbed followed by GC-MS analysis (Agilent 6890A–Thermo Focus DSQII). VOCs were manually selected in the chromatogram and standardized to an internal standard (toluene-d8). Only VOCs with a S/N-ratio>10 were used. Using SPSSv23, significant differences were searched and ROC-curves for discriminating MPM from all control groups were constructed. VOCs which had an AUCROC>0.80 are reported. 114 VOCs were selected of which 17 were significantly different between MPM patients and controls. Of these, 7 had AUCROC>0.80 and are possible markers for MPM diagnosis. The large discriminative power and good sensitivity and specificity imply the possibility to use breath analysis for MPM screening. Therefore, persons exposed to asbestos with a positive test should be considered for follow-up in a cost-effective way, decreasing the need for CT-scans and radiation exposure in low-risk persons. Further work includes combining models for discrimination and validating these findings.

Mesothelin (MSLN) methylation and soluble mesothelin-related protein levels in a Chinese asbestos-exposed population.

This study investigated the mesothelin (MSLN) methylation and its relationship with soluble mesothelin-related protein (SMRP) levels in participants stratified by asbestos exposure scenarios and benign asbestos-related diseases (ARDs). The presence of benign ARDs was confirmed through chest X-ray and the asbestos exposure history was obtained using a standardized questionnaire in this study, including 262 participants. Sera SMRP were measured using MESOMARK, and MSLN methylation in genomic DNA extracted from whole blood was detected by real-time methylation-specific PCR. Covariates were compared with SMRP concentrations using correlation analysis and the potential covariates affecting SMRP were determined by multiple linear regression analysis, and the distribution of methylation status was analyzed by Chi-square test. There was a trend toward elevation of SMRP values in healthy individuals exposed to asbestos as compared with those without asbestos exposure. The highest median level of SMRP was 1.3nM in subjects with asbestosis, followed by cases with pleura plaque and asbestosis (1.2nM), pleura plaque (0.9nM), healthy subjects with occupational exposure (0.9nM), non-occupational exposure (0.8nM), and mixed exposure (0.8nM). Within asbestosis cases, those with higher profusion scores had higher SMRP values than those with lower profusion scores (1.6 vs. 0.8nM). Based on multi-regression analysis, the trend toward elevation of SMRP remained significant in subjects with occupational exposure or in those with asbestosis, as compared with healthy subjects without exposure (p<0.01), although body mass index had an effect on SMRP (p<0.0001). Regardless of the differences in SMRP levels among these subgroups, MSLN methylation ranged from 80.5 to 92.5%, with no significant difference. The elevated level of SMRP in asbestosis with higher profusion scores could not be attributed to low MSLN methylation status. Our findings suggest that the elevation of SMRP is related to asbestos exposure and benign ARDs especially for cases with high profusion scores, which is independent of MSLN methylation.

Serum Biomarkers in Patients with Mesothelioma and Pleural Plaques and Healthy Subjects Exposed to Naturally Occurring Asbestos

This study investigated the diagnostic accuracy of the serum biomarkers osteopontin and mesothelin in discriminating mesothelioma patients from those with other, benign conditions and whether levels of the biomarkers differed in subjects who had inhaled naturally occurring asbestos compared with a non-exposed control group. This cross-sectional study studied 24 subjects with mesothelioma, 279 subjects with pleural plaques, 123 "healthy exposed," and 120 control subjects. The Kruskal-Wallis test was performed to compare mesothelin and osteopontin levels of the groups, and receiver operating characteristics curves were generated to determine diagnostic yields of both biomarkers. Multiple linear regression analyses were used to identify associated covariates with osteopontin and mesothelin levels. Serum osteopontin and mesothelin levels were higher in mesothelioma than in benign asbestos-related diseases and healthy exposed subjects. Both biomarker levels were independently associated with mesothelioma, age and smoking pack years. Mesothelin levels were also associated with body mass index. The sensitivity and specificity of osteopontin in distinguishing mesothelioma from the three other groups were 75 and 86%, respectively; those of mesothelin were 58 and 83%, respectively. The sensitivity and specificity to discriminate mesothelioma from pleural plaques and healthy subjects were 93 and 73%, respectively, if osteopontin and mesothelin levels were higher than their optimal cut off levels. The combination of serum osteopontin and mesothelin levels can help to distinguish mesothelioma from benign asbestos-related diseases and asbestos-exposed subjects.

Changes of mesothelin and osteopontin levels over time in formerly asbestos-exposed power industry workers

In patients developing malignant pleural mesothelioma (MPM) or lung cancer, using effective tumour markers is the quickest way to ensure early diagnosis and improve survival time. The aim of our study was to assess the influence of age and asbestos exposure on the blood levels of the proposed tumour markers, mesothelin and osteopontin, and to determine the change of these markers over time. We analysed 3,329 blood samples of 2,262 participants including 1,894 formerly asbestos-exposed power industry workers, a mixed group of 266 participants with an unknown history of asbestos exposure and a group of 102 non-asbestos-exposed controls. Marker concentrations were determined using commercial ELISA kits. While age had a strong influence on marker levels, there was no association between exposure duration or benign asbestos-related disease and marker levels. In order to assess the maximum increase that can be expected to occur in asbestos-exposed workers those with an at least 10 % increase were selected (n = 290 for mesothelin and n = 81 for osteopontin). The 95th percentile of the annual change was 0.402 nmol/l for mesothelin and 334 ng/ml for osteopontin. In two patients with MPM and five with lung cancer, we could obtain more than one marker result before the diagnosis was made. Both MPM patients showed a steep increase of mesothelin levels. Fixed cut-off values for deciding between intensive clinical work-up and continued surveillance appeared inadequate for the evaluated markers. While general conclusions cannot be drawn, we can say that the results of the two patients would be consistent with a mesothelin increase between 6 and 18 months before clinical symptoms developed.

A breath test for malignant mesothelioma using an electronic nose

Malignant mesothelioma (MM) is a rare tumour which is difficult to diagnose in its early stages. Earlier detection of MM could potentially improve survival. Exhaled breath sampling of volatile organic compounds (VOCs) using a carbon polymer array (CPA) electronic nose recognises specific breath profiles characteristic of different diseases, and can distinguish between patients with lung cancer and controls. With MM, the potential confounding effect of other asbestos-related diseases (ARDs) needs to be considered. We hypothesised that as CPA electronic nose would distinguish patients with MM, patients with benign ARDs, and controls with high sensitivity and specificity. 20 MM, 18 ARD and 42 control subjects participated in a cross-sectional, case-control study. Breath samples were analysed using the Cyranose 320 (Smiths Detection, Pasadena, CA, USA), using canonical discriminant analysis and principal component reduction. 10 MM subjects created the training set. Smell prints from 10 new MM patients were distinguished from control subjects with an accuracy of 95%. Patients with MM, ARDs and control subjects were correctly identified in 88% of cases. Exhaled breath VOC profiling can accurately distinguish between patients with MM, ARDs and controls using a CPA electronic nose. This could eventually translate into a screening tool for high-risk populations.

Osteopontin, asbestos exposure and pleural plaques: a cross-sectional study

BackgroundOsteopontin (OPN) is a plasma protein/cytokine produced in excess in several malignancies. In a recent study OPN was reported as being related to the duration of asbestos exposure and presence of benign asbestos-related diseases; however, it was unclear whether this protein was an indicator of exposure or effect.MethodsIn 193 workers, 50 with pleural plaques (PP), in whom different indicators of past asbestos exposure were estimated, OPN plasma levels were assessed using commercial quantitative sandwich enzyme immunoassays according to the manufacturer's instructions.ResultsOsteopontin increased with increasing age and several aspects of asbestos exposure, without differences related to the presence of pleural plaques. At multivariable regression analysis, the explanatory variables with a significant independent influence on OPN were length of exposure (positive correlation) and time elapsed since last exposure (positive correlation).ConclusionsSince asbestos in lung tissue tends to wane over time, OPN should decrease (rather than increase) with time since last exposure. Therefore, OPN cannot be a reliable biomarker of exposure nor effect (presence of pleural plaques).

Benign Asbestos-Related Pleural Disease

La silicosis es una enfermedad crónica progresiva producida por la inhalación de sílice cristalina. La mayoría de los casos aparecen en trabajadores de minería de interior y extracción de piedra natural (pizarra, granito). Ante la progresiva aparición de nuevos casos de silicosis en trabajadores con conglomerados artificiales de cuarzo (CAC), se planteó un estudio que tuvo como objetivo analizar las características de la silicosis producida por un nuevo agente en España.El estudio consistió en una serie de 96 casos diagnosticados de silicosis según criterios internacionales durante el periodo comprendido entre 2010 y 2017. Se analizaron las características clínicas, radiológicas, funcionales y patológicas.La edad media fue de 45 años, el 55% con silicosis simple y el 45% con silicosis complicada. En 10 pacientes se diagnosticó silicosis acelerada, con una media de 33 años de edad. El tiempo medio de exposición a los conglomerados fue de 15 años y en un 77% no se utilizaban medidas de protección adecuadas. La mitad de los pacientes estaban asintomáticos y presentaban diferentes formas clásicas en la radiografía de tórax y tomografía computarizada de alta resolución de tórax, así como imágenes de vidrio deslustrado. No se observaron alteraciones en la función pulmonar.La silicosis en los trabajadores con CAC se observa en personas jóvenes, en activo, en un considerable porcentaje de forma acelerada, con escasos síntomas y sin alteración funcional. Las medidas de protección son escasas. Es importante conocer estas características para el diagnóstico precoz y las necesarias medidas preventivas.Silicosis is a chronic progressive disease caused by inhalation of crystalline silica. Most cases develop in underground mine workers and in subjects involved in the extraction of natural stone (slate and granite). In view of the progressive emergence of new cases of silicosis in artificial quartz conglomerate workers, we performed a study to analyze the characteristics of silicosis produced by this new agent in Spain.The study consisted of a series of 96 cases of silicosis diagnosed according to international criteria during the period 2010-2017. We analyzed clinical, radiological, pathological and functional characteristics.Mean age of participants was 45 years; 55% had simple silicosis and 45% had complicated silicosis. Ten patients were diagnosed with accelerated silicosis, with a mean age of 33 years. Mean time of exposure to conglomerates was 15 years, and 77% had not used appropriate protection measures. Half of the patients were asymptomatic and presented different classic forms on chest X-ray and chest high-resolution computed tomography, along with ground-glass images. No lung function changes were recorded.Silicosis in artificial quartz conglomerate workers occurs in a young, actively employed population, a considerable percentage of whom present an accelerated form. They have few symptoms and no functional limitations. Protection measures are scarce. It is important to characterize these features to provide early diagnosis and implement the necessary preventive measures.

Hyperventilation in men claiming compensation for benign asbestos-related diseases

The observation that hyperventilation was common in men involved in civil court actions compared with my non-medico-legal practice stimulated me to carefully assess 100 consecutively seen men with non-malignant asbestos-related disease(s). A diagnosis of hyperventilation was made in 33 and probable hyperventilation in 12. The development of anxiety symptoms in these men could, in part at least, be prevented or greatly decreased if more emphasis was placed on the education of ex-asbestos workers by solicitors and organisations responsible for the initiation of civil actions.

Evaluation of ovarian cancer biomarkers in subjects with benign asbestos-related pleural diseases

Mesothelioma and ovarian cancer have been reported to have a similar pathogenesis, and for this reason it was hypothesized that there may be biomarkers in common and possibly associated with benign pleural diseases caused by asbestos exposure. Serum biomarkers including insulin-like growth factor-II (IGF-II), leptin, prolactin and vascular endothelial growth factor (VEGF) were measured in an observational study of subjects with benign asbestos-related pleural diseases (BARPD) (n=24) and healthy subjects with an asbestos exposure history (n=12). Mean serum IGF-II and VEGF concentration in healthy subjects with a history of asbestos exposure were higher than those with BARPD. Mean serum concentrations of leptin and prolactin showed opposite trends when compared to IGF-II and VEGF concentrations among these groups. The results suggest that IGF-II and VEGF concentrations are lower in BARPD, similar to studies of ovarian cancer. This finding warrants further investigation with malignant asbestos-related diseases.

Preliminary study of positron emission tomography/computed tomography and plasma osteopontin levels in patients with asbestos-related pleural disease

The aim of this study was to compare the results of semiquantitative analysis by(18)F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) with plasma osteopontin levels in the same asbestos-related pleural disease population. A total of 17 patients with asbestos-related pleural disease were prospectively recruited. They underwent PET/CT, and plasma osteopontin levels were measured. The maximum standardized uptake value (SUVmax) was determined from the most active pleural lesion in each patient. Malignant pleural mesothelioma (MPM) was histologically proven in 6 patients, and 11 patients had proven benign asbestos-related pleural diseases (7 pleural plaques, 4 asbestos pleurisy). Significant differences in SUVmax were found between patients with MPM and those with asbestos pleurisy (P = 0.031) and between patients with MPM and those with pleural plaques (P = 0.012). A significant difference was found in the plasma osteopontin levels between patients with asbestos pleurisy and patients with pleural plaques (Bonferroni correction, P = 0.024). The SUVmax in patients with benign asbestos-related diseases was statistically positively correlated with plasma osteopontin in the same group (Spearman's r = 0.75, P < 0.05). PET/CT might be more helpful than plasma osteopontin for distinguishing benign asbestos-related pleural diseases from MPM, and the SUVmax in benign asbestos-related pleural diseases may reflect changes in pleural inflammation.

Clinical Significance of Serum Vascular Endothelial Growth Factor in Malignant Pleural Mesothelioma

Malignant pleural mesothelioma (MPM) is an aggressive malignant tumor of mesothelial origin associated with asbestos exposure. MPM has a limited response to conventional chemotherapy and radiotherapy so diagnosing MPM early is very important. Vascular endothelial growth factor (VEGF) is an autocrine growth factor for MPM. Here, we investigated the serum levels of VEGF in patients with MPM in comparison with a population that had been exposed to asbestos without developing MPM. Serum concentrations of VEGF were measured in 51 patients with MPM and 42 individuals with benign asbestos-related diseases (asbestosis or pleural plaques) or who were healthy despite asbestos exposure. We demonstrated that patients with MPM had significantly higher serum levels of VEGF than a population who had been exposed to asbestos but had not developed MPM, and the patients with advanced stage MPM showed higher levels of VEGF than the early stage patients with MPM. The difference in overall survival between the groups with VEGF serum levels lower and higher than the assumed cutoff of 460 pg/ml was significant. Our data suggest that the VEGF serum concentration could be a useful marker for screening MPM among asbestos-exposed individuals and as a prognostic factor.

Diagnostic Performance of Soluble Mesothelin and Megakaryocyte Potentiating Factor in Mesothelioma

Soluble mesothelin (SM) is currently the reference serum biomarker of malignant pleural mesothelioma (MPM). Megakaryocyte potentiating factor (MPF), which originates from the same precursor protein, is potentially more sensitive, yet lacks validation. To analyze the diagnostic performance of MPF as an MPM biomarker and compare this performance with SM. A total of 507 participants were enrolled in six cohorts: healthy control subjects (n = 101), healthy asbestos-exposed individuals (n = 89), and patients with benign asbestos-related disease (n = 123), benign respiratory disease (n = 46), lung cancer (n = 63), and MPM (n = 85). Sera were analyzed for SM and MPF levels using the Mesomark and Human MPF ELISA kit, respectively. SM and MPF levels differed significantly between patients with MPM and participants from each other cohort (P < 0.001). Receiver operating characteristics curve analysis did not reveal a significant difference between both markers in area under curve (AUC) for distinguishing MPM from all cohorts jointly (SM = 0.871, MPF = 0.849; P = 0.28). At 95% specificity, SM and MPF had a sensitivity of 64% (cutoff = 2.00 nmol/L) and 68% (cutoff = 12.38 ng/ml), respectively. Combining both markers did not improve the diagnostic performance. In this prospective multicenter study, MPF is validated as a highly performant MPM biomarker. The similar AUC values of SM and MPF, together with the limited difference in sensitivity, show that both serum biomarkers have an equivalent diagnostic performance.

Anzeigekriterien asbestfaserstaubbedingter Erkrankungen gemäß BK-Nr. 4103 BKV

Asbestos-related diseases still play an important role in occupational medicine. The detection of benign asbestos-related diseases is one condition for the compensation of asbestos-related lung cancer in Germany. Due to the increasing use of computed tomography, asbestos-related diseases are more frequently detected in the early stages. The present article proposes recommendations for the findings which have to be reported as suspicious for being asbestos-related based on a) chest X-rays and b) computed tomography using the International Classification System for Occupational and Environmental Respiratory Diseases (ICOERD).

Asbestos exposure and benign asbestos diseases in 772 formerly exposed workers: Dose–response relationships

Since previous studies have provided conflicting results, we investigated the relationship between the risk of benign asbestos-related diseases and different aspects of asbestos exposure in previous asbestos workers who underwent low-dose computed tomography (CT). CT scans were carried out in 772 subjects. A questionnaire was employed to collect data on smoking habits and duration, peak and cumulative exposure, and time since first exposure to asbestos. Multiple logistic regression models with stepwise selection of variables were used to evaluate the associations. Fourteen (1.8%) cases of asbestosis, 187 (24.2%) of pleural plaques (PP), and 50 (6.5%) of diffuse pleural thickening (DPT) were found. The significant risk factors were: cumulative exposure for asbestosis (P for trend = 0.004); time since first exposure (P for trend <0.001), and peak exposure (P for trend <0.001) for PP; and time since first exposure for DPT (P for trend = 0.024). Parenchymal asbestosis and PP are associated with different aspects of asbestos exposure. DPT appears to be less specific for asbestos exposure.

Comparison of Osteopontin, Megakaryocyte Potentiating Factor, and Mesothelin Proteins as Markers in the Serum of Patients with Malignant Mesothelioma

There is increasing interest in identifying a blood-based marker for the asbestos-related tumor, malignant mesothelioma. Three potential markers for mesothelioma are mesothelin, megakaryocyte potentiating factor (MPF) and osteopontin. The purpose of the current study was to directly compare these biomarkers in the same sample population, determining their sensitivity and specificity in establishing a diagnosis, and to determine if diagnostic accuracy for mesothelioma is improved by combining the data from all three markers. Serum levels of mesothelin, MPF and osteopontin were determined by commercially available assays in 66 samples from patients with pleural malignant mesothelioma, 20 healthy individuals, 21 patients with asbestos-related lung or pleural disease, 30 patients presenting with benign pleural effusions and 30 patients with other malignancies. Serum levels of the three markers were elevated in mesothelioma patients. At a level of specificity of 95% relative to healthy controls and patients with benign asbestos related disease, the sensitivity for mesothelioma was 34% for MPF, 47% for osteopontin and 73% for mesothelin. Osteopontin and MPF were unable to differentiate patients with mesothelioma from patients with other malignancies or those presenting with transudative pleural effusions. Combining the data from the three biomarkers using a logistic regression model did not improve sensitivity for detecting mesothelioma above that of the mesothelin marker alone. Serum mesothelin remains the most specific marker for the diagnosis of mesothelioma.