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

BACKGROUND: 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. METHODS: 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). RESULTS: 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. CONCLUSIONS: 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.

[Chest high-resolution CT features analysis in predicting the progression of asbestosis].

Objective: To analyze the radiological characteristics of chest high-resolution computed tomography (HRCT) of patients with asbestosis, and to investigate the signs of predicting the disease progression of asbestosis. Methods: A prospective method was used to enroll 68 patients with asbestosis who were regularly followed up from 2013 to 2016. The radiological characteristics of patients with asbestosis were described by the International Classification of HRCT for Occupational and Environmental Respiratory Diseases (ICOERD) , and the differences between patients with and without progression were compared during the observation period. The Cox proportional hazards regression model was used to analyze the chest HRCT radiological signs predicting the progression of asbestosis. Results: The study included 68 patients with asbestosis aged (65.5±7.8) years old, of which 64.7% (44/68) were female, 29.4% (20/68) had a history of smoking. There was no significant difference in age, sex, smoking and asbestos exposure between patients with progressive asbestosis (20.6%, 14/68) and patients without progressive asbestosis (79.4%, 54/68) (P>0.05) . Chest HRCT of patients with asbestosis showed irregular and/or linear opacities, of which 5.9% (4/68) were accompanied by honeycombing. Irregular and/or linear opacities were mainly lower lung preponderant, often accompanied with ground glass opacity and mosaic perfusion. 98.5% (67/68) had pleural abnormalities, of which 39.7% (27/68) had diffuse pleural thickening with parenchymal bands and/or rounded atelectasis. The analysis of multivariable Cox proportional hazard regression showed that the risk of the progression of asbestosis was increased with higher irregular and/or linears opacities cores (HR=1.184, 95%CI: 1.012-1.384, P=0.034) and the appearance of honeycombing (HR=6.488, 95%CI: 1.447-29.097, P=0.015) . Conclusion: The irregular and/or linear opacities scores and honeycombing on chest HRCT are independent influencing factors for predicting the disease progression of asbestosis.

Chest high-resolution CT features analysis in predicting the progression of asbestosis / 中华劳动卫生职业病杂志

Objective: To analyze the radiological characteristics of chest high-resolution computed tomography (HRCT) of patients with asbestosis, and to investigate the signs of predicting the disease progression of asbestosis. Methods: A prospective method was used to enroll 68 patients with asbestosis who were regularly followed up from 2013 to 2016. The radiological characteristics of patients with asbestosis were described by the International Classification of HRCT for Occupational and Environmental Respiratory Diseases (ICOERD) , and the differences between patients with and without progression were compared during the observation period. The Cox proportional hazards regression model was used to analyze the chest HRCT radiological signs predicting the progression of asbestosis. Results: The study included 68 patients with asbestosis aged (65.5±7.8) years old, of which 64.7% (44/68) were female, 29.4% (20/68) had a history of smoking. There was no significant difference in age, sex, smoking and asbestos exposure between patients with progressive asbestosis (20.6%, 14/68) and patients without progressive asbestosis (79.4%, 54/68) (P>0.05) . Chest HRCT of patients with asbestosis showed irregular and/or linear opacities, of which 5.9% (4/68) were accompanied by honeycombing. Irregular and/or linear opacities were mainly lower lung preponderant, often accompanied with ground glass opacity and mosaic perfusion. 98.5% (67/68) had pleural abnormalities, of which 39.7% (27/68) had diffuse pleural thickening with parenchymal bands and/or rounded atelectasis. The analysis of multivariable Cox proportional hazard regression showed that the risk of the progression of asbestosis was increased with higher irregular and/or linears opacities cores (HR=1.184, 95%CI: 1.012-1.384, P=0.034) and the appearance of honeycombing (HR=6.488, 95%CI: 1.447-29.097, P=0.015) . Conclusion: The irregular and/or linear opacities scores and honeycombing on chest HRCT are independent influencing factors for predicting the disease progression of asbestosis.

Diagnosis of lung cancer: a necropsy-based study of 128 cases (1997-2016).

BACKGROUND: The diagnosis of lung cancer (LC) may be difficult to make in the elderly. We report on the diagnostic elements available in life in an LC necropsy case series of asbestos-exposed workers and describe the frequency of non-neoplastic asbestos-related diseases as biological exposure indices. METHODS: We reviewed pathologic and clinical records of an unselected series of autopsies (1997-2016) in patients with LC employed in the Monfalcone shipyards. We assessed the consistency with autopsy results of diagnoses based on, respectively, radiologic, cytologic, and histologic findings. RESULTS: Data on 128 autopsy-confirmed LC cases were available; in life, 119 had been diagnosed as LC. Among these, 49 had histologic confirmation of diagnosis (17 with immunophenotyping); histology had been negative in 4. Cytology had been the main positive finding and the basis for diagnosis in 24 cases, but had been negative in 13. Chest computed tomography had been the basis for diagnosis in 45; in 18 cases, it had been negative. Nine patients had received a diagnosis different from LC, among whom 4 had been suspected to have malignant pleural mesothelioma by chest computed tomography. Pleural plaques were found in 124 and histologic asbestosis in 46 cases. CONCLUSIONS: Autopsies confirmed all LC diagnoses received in life, including 46 that would have been considered only possible LC based on clinical workup. The overall survival in this case series was poor. The high prevalence of pleural plaques and asbestosis suggest severity of asbestos exposures.

3-Dimensional Quantification of Composite Pleural Plaque Volume in Patients Exposed to Asbestos Using High-resolution Computed Tomography: A Validation Study.

RATIONALE: As pleural plaque has been reported as a risk factor in the occurrence of lung cancer and mesothelioma, a reproducible and precise method of measurement of pleural plaque volume (PPV) is needed to further describe these relationships. The aim of the study was to assess the reproducibility of a 3-dimensional computed tomography (3D-CT) volumetric analysis of PPV in patients with occupational exposure to asbestos. MATERIAL AND METHODS: A total of 28 patients were retrospectively randomly selected from the multicenter APEXS (Asbestos Post Exposure Survey) study, which was held between 2003 and 2005. All patients underwent a 3D-CT scan. Two readers specialized in chest radiology completed the 3D semiautomated quantification of lung volume using dedicated software. They also had to categorize the visual extent of pleural plaque in terms of thickness and circumference. Reproducibility of the continuous PPV variable was assessed using the intraclass correlation coefficient (ICC) and Bland-Altman analysis. Reproducibility of categorical variables was assessed using the κ test. RESULTS: Intraobserver reproducibility of PPV was almost perfect (ICC=0.98 [95% interval: 0.97-0.99]), and interobserver reproducibility was very good (ICC=0.93 [0.88-0.97]). At Bland-Altman analysis, the mean differences were 0.1 (limit of agreement: -11.0 to 11.2) and 3.7 cc (-17.8 to 25.2), respectively. Visual analysis of both plaque in terms of thickness and circumference were fair to moderate, with κ values ranging from 0.30 to 0.60. CONCLUSIONS: 3D semiautomatic quantification of PPV is feasible and reproducible using CT in patients with occupational exposure to asbestos. PPV measurement may be useful to correlate with other asbestos-related disease outcomes and prognosis.

Pleural adverse drugs reactions and protein kinase inhibitors: Identification of suspicious targets by disproportionality analysis from VigiBase.

AIMS: To evaluate the risk of pleural disorders (PD) associated with 33 protein kinase (PK) inhibitors (PKIs) through a disproportionality analysis and to identify which PKs and pathways are involved in PKI-induced PD. METHODS: To evaluate the risk of PD, reporting odds ratios (RORs) were calculated for 33 PKIs through data registered in the World Health Organization safety report database (VigiBase). We undertook a literature review to identify PKs that were possibly involved in PD caused by PKIs. Pearson correlation coefficients (r) between RORs and affinity data of 19 PKIs were calculated to identify the cellular target most likely to be involved in PKI-induced PD. RESULTS: A total of 235 110 individual case safety reports were extracted from the database for 33 available PKIs. Among these reports, 5001 concerned PD (2.1%). Significant and positive disproportionality for PD was found for 29 of 33 PKI included in our study with top values for dasatinib [ROR = 115.3; 95% confidence interval (CI): 110.1-120.8], bosutinib (ROR = 20.4; 95% CI: 15.8-26.4) and ponatinib (ROR = 12; 95% CI: 9.2-15.6). Correlation analyses between the product of dissociation constant and ROR highlighted possibly Lyn involvement in PD with PKI (r = 0.73, P = 0.0004). CONCLUSIONS: Our study showed that 28 of the 33 tested PKIs were associated with PD. Besides, the study highlighted the role of Lyn in PD caused by PKIs through an immune-mediated process.

Pleural abnormalities and exposure to elongate mineral particles in Minnesota iron ore (taconite) workers.

BACKGROUND: Iron ore (taconite) mining and processing are an important industry in northern Minnesota and western Michigan. Concerns around exposures have centered largely on exposure to non-asbestiform amphibole elongate mineral particles (EMPs) found in the eastern portion of the Minnesota iron range. METHODS: A cross sectional survey was undertaken of current and former taconite workers and spouses along with a detailed exposure assessment. Participants provided an occupational history and had a chest radiograph performed. RESULTS: A total of 1188 workers participated. Potential exposures to non-amphibole EMPs were evident across multiple jobs in all active mines. Pleural abnormalities were found in 16.8% of workers. There was an association of pleural abnormalities with cumulative EMP exposure that was not specific to the eastern portion of the range. CONCLUSION: There was evidence of a mild to moderate increase in pleural abnormalities in this population of miners, associated with geographically non-specific cumulative EMP exposure.

Targeting plasminogen activator inhibitor-1 in tetracycline-induced pleural injury in rabbits.

Elevated active plasminogen activator inhibitor-1 (PAI-1) has an adverse effect on the outcomes of intrapleural fibrinolytic therapy (IPFT) in tetracycline-induced pleural injury in rabbits. To enhance IPFT with prourokinase (scuPA), two mechanistically distinct approaches to targeting PAI-1 were tested: slowing its reaction with urokinase (uPA) and monoclonal antibody (mAb)-mediated PAI-1 inactivation. Removing positively charged residues at the "PAI-1 docking site" (179RHRGGS184→179AAAAAA184) of uPA results in a 60-fold decrease in the rate of inhibition by PAI-1. Mutant prourokinase (0.0625-0.5 mg/kg; n = 12) showed efficacy comparable to wild-type scuPA and did not change IPFT outcomes ( P > 0.05). Notably, the rate of PAI-1-independent intrapleural inactivation of mutant uPA was 2 times higher ( P < 0.05) than that of the wild-type enzyme. Trapping PAI-1 in a "molecular sandwich"-type complex with catalytically inactive two-chain urokinase with Ser195Ala substitution (S195A-tcuPA; 0.1 and 0.5 mg/kg) did not improve the efficacy of IPFT with scuPA (0.0625-0.5 mg/kg; n = 11). IPFT failed in the presence of MA-56A7C10 (0.5 mg/kg; n = 2), which forms a stable intrapleural molecular sandwich complex, allowing active PAI-1 to accumulate by blocking its transition to a latent form. In contrast, inactivation of PAI-1 by accelerating the active-to-latent transition mediated by mAb MA-33B8 (0.5 mg/kg; n = 2) improved the efficacy of IPFT with scuPA (0.25 mg/kg). Thus, under conditions of slow (4-8 h) fibrinolysis in tetracycline-induced pleural injury in rabbits, only the inactivation of PAI-1, but not a decrease in the rate of its reaction with uPA, enhances IPFT. Therefore the rate of fibrinolysis, which varies in different pathologic states, could affect the selection of PAI-1 inhibitors to enhance fibrinolytic therapy.

The Effects of Pleural Plaques on Longitudinal Lung Function in Vermiculite Miners of Libby, Montana.

BACKGROUND: This study was conducted to assess associations of pleural plaques (PP) and longitudinal lung function in vermiculite miners of Libby, Montana who are occupationally exposed to asbestos. High-resolution computed tomography (HRCT) was used to identify asbestos-related findings in former Libby vermiculite miners. We investigated annual lung function decline in miners with PP only and compared them to miners with normal HRCT findings. MATERIALS AND METHODS: HRCTs from 128 miners were categorized into the following 4 diagnostic groups: (1) normal computed tomography scan (n = 9); (2) PP only (n = 72); (3) PP and interstitial fibrosis (n = 26) and (4) additional HRCT abnormalities (n = 21) such as rounded atelectasis, diffuse pleural thickening, pleural effusions or pulmonary nodules or tumor >1cm in diameter. Random intercept and slope linear mixed-effect regression models identified differences in lung function decline between miners with asbestos-associated outcomes and those with normal HRCT. Models were adjusted for follow-up time, body mass index, smoking status, latent exposure period and employment years. Interactions for smoking status with age and smoking status with pleural plaque severity were examined. RESULTS: Miners with PP only did not have an accelerated decline in lung function between 40 and 80 years. Miners with PP and additional HRCT abnormalities displayed significantly accelerated declines in forced expiratory volume in 1 second and diffusing capacity of the lungs for carbon monoxide (P = 0.05 and P < 0.01, respectively). Plaque severity did not affect lung function decline. However, smokers with extensive plaques displayed accelerated loss in diffusing capacity of the lungs for carbon monoxide and forced expiratory volume in 1 second when compared to nonsmoking miners with mild plaque formation. CONCLUSIONS: PP alone did not significantly affect lung function decline in vermiculite miners of Libby, Montana.

Incidental and Underreported Pleural Plaques at Chest CT: Do Not Miss Them-Asbestos Exposure Still Exists.

Pleural plaques (PPs) may be a risk factor for mortality from lung cancer in asbestos-exposed workers and are considered to be a marker of exposure. Diagnosing PPs is also important because asbestos-exposed patients should be offered a health surveillance that is mandatory in many countries. On the other hand PPs are useful for compensation purposes. In this study we aimed to evaluate the prevalence, as incidental findings, and the underreporting rate of PPs in chest CT scans (CTs) performed in a cohort of patients (1512) who underwent chest CT with a slice thickness no more than 1.25 mm. PPs were found in 76 out of 1482 patients (5.1%); in 13 out of 76 (17,1%) CTs were performed because of clinical suspicion of asbestos exposure and 5 of them (38%) were underreported by radiologist. In the remaining 63 cases (82.9%) there was no clinical suspicion of asbestos exposure at the time of CTs (incidental findings) and in 38 of these 63 patients (60.3%) PPs were underreported. Reaching a correct diagnosis of PPs requires a good knowledge of normal locoregional anatomy and rigorous technical approach in chest CT execution. However the job history of the patient should always be kept in mind.

Long-term epidemiological observation of asbestos-related diseases in Poland, 1970-2015.

BACKGROUND: Occupational exposure to asbestos constitutes a major public health concern. Despite this in many countries, data and registration systems for occupational asbestos-related diseases are non-existent or poorly developed. AIMS: To analyse the incidence of occupational asbestos-related diseases in Poland between the years 1970 and 2015, with particular emphasis on the periods after introduction of a ban on asbestos and following introduction of a surveillance programme. METHODS: Analysis based on all medically recognized cases, certified as occupational diseases and reported obligatorily from all over the country to the Central Register of Occupational Diseases. RESULTS: During the period 1970-2015, 4983 cases were reported as asbestos-related diseases. The most prevalent were asbestosis, lung cancer, diseases of pleura or pericardium and mesothelioma. A considerable increase in the number of such cases from the beginning of their registration until 2004 occurred after introduction of the Amiantus programme, a nationwide programme of periodic medical examinations for former asbestos workers. CONCLUSIONS: Introduction of a medical surveillance programme improved case recognition and allowed a more reliable estimate of the number of reported asbestos-related diseases.

Diagnostic Performance of Ultra-Low-Dose Computed Tomography for Detecting Asbestos-Related Pleuropulmonary Diseases: Prospective Study in a Screening Setting.

OBJECTIVE: To evaluate the diagnostic performance of Ultra-Low-Dose Chest CT (ULD CT) for the detection of any asbestos-related lesions (primary endpoint) and specific asbestos-related abnormalities, i.e. non-calcified and calcified pleural plaques, diffuse pleural thickening, asbestosis and significant lung nodules (secondary endpoints). MATERIAL AND METHODS: 55 male patients (55.7±8.1 years old) with occupational asbestos exposure for at least 15 years and where CT screening was indicated were prospectively included. They all underwent a standard unenhanced chest CT (120kV, automated tube current modulation), considered as the reference, and an ULD CT (135kV, 10mA), both with iterative reconstruction. Two chest radiologists independently and blindly read the examinations, following a detailed protocol. Sensitivity, specificity, positive predictive value, negative predictive value, accuracy and error rate of ULD CT were calculated using the exact method of Pearson with a confidence interval of 95%. RESULTS: Radiation dose was 17.9±1.2mGy.cm (0.25mSv) for the ULD-CT versus 288.8 ±151mGy.cm (4mSv); p <2.2e-16. Prevalence of abnormalities was 20%. The ULD CT's diagnostic performance in joint reading was high for the primary endpoint (sensitivity = 90.9%, specificity = 100%, positive predictive value = 100%, negative predictive value = 97.8%), high for lung nodules, diffuse pleural thickening and calcified pleural plaques (sensitivity, specificity, PPV and NPV = 100%) and fair for asbestosis (sensitivity = 75%, specificity = 100%, PPV = 00%, NPV = 98.1%). Intra-reader accuracy between the ULD CT and the reference CT for the primary endpoint was 98% for the senior and 100% for the junior radiologist. Inter-reader agreement for the primary endpoint was almost perfect (Cohen's Kappa of 0.81). CONCLUSION: ULD CT in the screening of asbestos exposure related diseases has 90.9% sensitivity and 100% specificity, and could therefore be proposed as a first line examination.

Pleuroparenchymal fibroelastosis associated with aluminosilicate dust: a case report.

Idiopathic pleuroparenchymal fibroelastosis (IPPFE) is a recently described rare condition, characterized by pleural and subpleural parenchymal fibrosis, predominantly in the upper lobes. The clinical course of this disease is progressive and prognosis is poor, with little information regarding the etiology of IIPPFE. This report describes an IPPFE patient with convincing evidence of inhalational dust and suggests that dust exposure should be considered as a new causative factor of IPPFE.

Occupational lung disease survey of respiratory physicians in Northern Ireland.

BACKGROUND: Respiratory physicians are likely to encounter occupational lung disease (OLD) in their daily practice. AIMS: To assess the profile of cases being encountered by general respiratory physicians in Northern Ireland (NI) and determine satisfaction with training, confidence in diagnosis and management of OLD. METHODS: An online survey of all consultant respiratory physicians currently practising in NI. Questions assessed the numbers of new cases seen over the preceding year, case type, satisfaction with specialist registrar training in OLD and degree of confidence in the diagnosis and management of these conditions. RESULTS: Of the 40 consultants identified, the response rate was 80% (n = 32) with 94% of respondents (n = 30) indicating they had dealt with patients suspected of having occupation-related respiratory symptoms. The most commonly encountered OLDs were pleural plaques (91% of respondents), occupational asthma (88%), asbestosis (84%), non-asbestosis pulmonary fibrosis (76%), hypersensitivity pneumonitis (67%) and mesothelioma (66%). Just over one third of consultants (36%, n = 10) indicated a lack of confidence in diagnosis and management of OLD with almost half (48%) dissatisfied with OLD training as a registrar and a further 78% (n = 25) indicating they would value additional training in OLD as a consultant. CONCLUSIONS: The majority of respiratory consultants in NI encountered OLD in their day to day practice and half were dissatisfied with their specialist registrar training in OLD and express a lack of confidence in the diagnosis and management of these conditions. This highlights the need for additional training at both registrar and consultant level.