The European Respiratory Journal

About the journal

Publisher: European Respiratory Society
Published: 1988 to the present, England
Language: English
ISSN: 0903-1936 (print), 1399-3003 (electronic)
Merged from: Clinical Respiratory Physiology
Merged from: European Journal of Respiratory Diseases
Its record in the NLM Catalog

2020s

A randomised phase II study of extended pleurectomy/decortication preceded or followed by chemotherapy in patients with early-stage pleural mesothelioma: EORTC 1205. J. Raskin, V. Surmont, A.P.W.M. Maat, et al. 2024;63(6). Randomized trial PubMed · Publisher · Free full text

Abstract

Background: The role of surgery in pleural mesothelioma remains controversial. It may be appropriate in highly selected patients as part of a multimodality treatment including chemotherapy. Recent years have seen a shift from extrapleural pleuropneumonectomy toward extended pleurectomy/decortication. The most optimal sequence of surgery and chemotherapy remains unknown.

Methods: EORTC-1205-LCG was a multicentric, noncomparative phase 2 trial, 1:1 randomising between immediate (arm A) and deferred surgery (arm B), followed or preceded by chemotherapy. Eligible patients (Eastern Cooperative Oncology Group 0-1) had treatment-naïve, borderline resectable T1-3 N0-1 M0 mesothelioma of any histology. Primary outcome was rate of success at 20 weeks, a composite end-point including 1) successfully completing both treatments within 20 weeks; 2) being alive with no signs of progressive disease; and 3) no residual grade 3-4 toxicity. Secondary end-points were toxicity, overall survival, progression-free survival and process indicators of surgical quality.

Findings: 69 patients were included in this trial. 56 (81%) patients completed three cycles of chemotherapy and 58 (84%) patients underwent surgery. Of the 64 patients in the primary analysis, 21 out of 30 patients in arm A (70.0%; 80% CI 56.8-81.0%) and 17 out of 34 patients (50.0%; 80% CI 37.8-62.2%) in arm B reached the statistical end-point for rate of success. Median progression-free survival and overall survival were 10.8 (95% CI 8.5-17.2) months and 27.1 (95% CI 22.6-64.3) months in arm A, and 8.0 (95% CI 7.2-21.9) months and 33.8 (95% CI 23.8-44.6) months in arm B. Macroscopic complete resection was obtained in 82.8% of patients. 30- and 90-day mortality were both 1.7%. No new safety signals were found, but treatment-related morbidity was high.

Interpretation: EORTC 1205 did not succeed in selecting a preferred sequence of pre- or post-operative chemotherapy. Either procedure is feasible with a low mortality, albeit consistent morbidity. A shared informed decision between surgeon and patient remains essential.

Copyright ©The authors 2024.
ERS statement on benign pleural effusions in adults. A. Sundaralingam, E.M. Grabczak, P. Burra, et al. 2024;64(6). Guideline PubMed · Publisher

Abstract

The incidence of non-malignant pleural effusions far outweighs that of malignant pleural effusions and is estimated to be at least 3-fold higher. These so-called benign effusions do not follow a "benign course" in many cases, with mortality rates matching and sometimes exceeding those of malignant pleural effusions. In addition to the impact on patients, healthcare systems are also significantly affected, with recent US epidemiological data demonstrating that 75% of resource allocation for pleural effusion management is spent on non-malignant pleural effusions (excluding empyema). Despite this significant burden of disease, and by existing at the junction of multiple medical specialties, reflecting a heterogenous constellation of medical conditions, non-malignant pleural effusions are rarely the focus of research or the subject of management guidelines. With this European Respiratory Society Task Force, we assembled a multispecialty collaborative across 11 countries and three continents to provide a statement based on systematic searches of the medical literature to highlight evidence in the management of the following clinical areas: a diagnostic approach to transudative effusions, heart failure, hepatic hydrothorax, end-stage renal failure, benign asbestos-related pleural effusion, post-surgical effusion and nonspecific pleuritis.

Copyright ©The authors 2024. For reproduction rights and permissions contact [email protected].
Single-cell transcriptomic analysis of human pleura reveals stromal heterogeneity and informs in vitro models of mesothelioma. J. Obacz, J.A. Valer, R. Nibhani, et al. 2024;63(1). PubMed · Publisher · Free full text

Abstract

The pleural lining of the thorax regulates local immunity, inflammation and repair. A variety of conditions, both benign and malignant, including pleural mesothelioma, can affect this tissue. A lack of knowledge concerning the mesothelial and stromal cells comprising the pleura has hampered the development of targeted therapies. Here, we present the first comprehensive single-cell transcriptomic atlas of the human parietal pleura and demonstrate its utility in elucidating pleural biology. We confirm the presence of known universal fibroblasts and describe novel, potentially pleural-specific, fibroblast subtypes. We also present transcriptomic characterisation of multiple in vitro models of benign and malignant mesothelial cells, and characterise these through comparison with in vivo transcriptomic data. While bulk pleural transcriptomes have been reported previously, this is the first study to provide resolution at the single-cell level. We expect our pleural cell atlas will prove invaluable to those studying pleural biology and disease. It has already enabled us to shed light on the transdifferentiation of mesothelial cells, allowing us to develop a simple method for prolonging mesothelial cell differentiation in vitro.

Copyright ©The authors 2024.
Who is at risk of lung nodules on low-dose CT in a Western country? A population-based approach. J. Cai, M. Vonder, Y. Du, et al. 2024;63(6). PubMed · Publisher · Free full text

Abstract

Background: This population-based study aimed to identify the risk factors for lung nodules in a Western European general population.

Methods: We quantified the presence or absence of lung nodules among 12 055 participants of the Dutch population-based ImaLife (Imaging in Lifelines) study (age ≥45 years) who underwent low-dose chest computed tomography. Outcomes included the presence of 1) at least one solid lung nodule (volume ≥30 mm3) and 2) a clinically relevant lung nodule (volume ≥100 mm3). Fully adjusted multivariable logistic regression models were applied overall and stratified by smoking status to identify independent risk factors for the presence of nodules.

Results: Among the 12 055 participants (44.1% male; median age 60 years; 39.9% never-smokers; 98.7% White), we found lung nodules in 41.8% (5045 out of 12 055) and clinically relevant nodules in 11.4% (1377 out of 12 055); the corresponding figures among never-smokers were 38.8% and 9.5%, respectively. Factors independently associated with increased odds of having any lung nodule included male sex, older age, low educational level, former smoking, asbestos exposure and COPD. Among never-smokers, a family history of lung cancer increased the odds of both lung nodules and clinically relevant nodules. Among former and current smokers, low educational level was positively associated with lung nodules, whereas being overweight was negatively associated. Among current smokers, asbestos exposure and low physical activity were associated with clinically relevant nodules.

Conclusions: The study provides a large-scale evaluation of lung nodules and associated risk factors in a Western European general population: lung nodules and clinically relevant nodules were prevalent, and never-smokers with a family history of lung cancer were a non-negligible group.

Copyright ©The authors 2024.
A spatially restricted fibrotic niche in pulmonary fibrosis is sustained by M-CSF/M-CSFR signalling in monocyte-derived alveolar macrophages. N. Joshi, S. Watanabe, R. Verma, et al. 2020;55(1). PubMed · Publisher · Free full text

Abstract

Ontologically distinct populations of macrophages differentially contribute to organ fibrosis through unknown mechanisms.We applied lineage tracing, single-cell RNA sequencing and single-molecule fluorescence in situ hybridisation to a spatially restricted model of asbestos-induced pulmonary fibrosis.We demonstrate that tissue-resident alveolar macrophages, tissue-resident peribronchial and perivascular interstitial macrophages, and monocyte-derived alveolar macrophages are present in the fibrotic niche. Deletion of monocyte-derived alveolar macrophages but not tissue-resident alveolar macrophages ameliorated asbestos-induced lung fibrosis. Monocyte-derived alveolar macrophages were specifically localised to fibrotic regions in the proximity of fibroblasts where they expressed molecules known to drive fibroblast proliferation, including platelet-derived growth factor subunit A. Using single-cell RNA sequencing and spatial transcriptomics in both humans and mice, we identified macrophage colony-stimulating factor receptor (M-CSFR) signalling as one of the novel druggable targets controlling self-maintenance and persistence of these pathogenic monocyte-derived alveolar macrophages. Pharmacological blockade of M-CSFR signalling led to the disappearance of monocyte-derived alveolar macrophages and ameliorated fibrosis.Our findings suggest that inhibition of M-CSFR signalling during fibrosis disrupts an essential fibrotic niche that includes monocyte-derived alveolar macrophages and fibroblasts during asbestos-induced fibrosis.

Copyright ©ERS 2020.
Cancer in the time of COVID-19: expert opinion on how to adapt current practice. J. Raskin, M. Lebeer, C. De Bondt, et al. 2020;55(5). Letter PubMed · Publisher · Free full text

Abstract

Our current thoracic oncology practice could/should be adapted to the COVID-19 pandemic by reducing time in hospital and patient contacts with healthcare workers, whilst maintaining quality of care. This letter offers expert advice on how to do so. https://bit.ly/2JR2IoT

2010s

Asbestos-related lung cancers are rarely associated with ALK, ROS1 and RET rearrangements. M. Uguen, J.D. Dewitte, B. Loddé, et al. 2018;51(3). Letter · Comment PubMed · Publisher
Investigating unilateral pleural effusions: the role of cytology. D.T. Arnold, D. De Fonseka, S. Perry, et al. 2018;52(5). PubMed · Publisher

Abstract

The vast majority of undiagnosed unilateral pleural effusions have fluid sent for cytological analysis. Despite widespread use, there is uncertainty about its sensitivity to diagnose malignant pleural effusions (MPEs). Our aim was to ascertain the utility of cytology using a large prospective cohort.Consecutive patients presenting with an undiagnosed unilateral pleural effusion were recruited to this UK-based study. All had pleural fluid sent for cytological analysis. Cytological sensitivity was based on the final diagnosis at 12 months, confirmed by two consultants.Over 8 years, 921 patients were recruited, of which 515 had a MPE. Overall sensitivity of fluid cytology to diagnose malignancy was 46% (95% CI 42-58%). There was variation in sensitivity depending on cancer primary, with mesothelioma (6%) and haematological malignancies (40%) being significantly lower than adenocarcinomas (79%). MPEs secondary to ovarian cancer had high pick-up rates (95%). In asbestos-exposed males with exudative effusions, the risk of MPE was 60%, but cytological sensitivity was 11%.This is the largest prospective study of pleural fluid cytology and informs discussions with patients about the likely requirement for investigations following thoracentesis. In patients presenting with a clinical suspicion of mesothelioma, cytological sensitivity is low, so more definitive investigations could be performed sooner.

Copyright ©ERS 2018.
Association between lung cancer somatic mutations and occupational exposure in never-smokers. C. Paris, P. Do, B. Mastroianni, et al. 2017;50(4). PubMed · Publisher

Abstract

Occupational exposure constitutes a common risk factor for lung cancer. We observed molecular alterations in 73% of never-smokers, 35% of men and 8% of women were exposed to at least one occupational carcinogen. We report herein associations between molecular patterns and occupational exposure.BioCAST was a cohort study of lung cancer in never-smokers that reported risk factor exposure and molecular patterns. Occupational exposure was assessed via a validated 71-item questionnaire. Patients were categorised into groups that were unexposed and exposed to polycyclic aromatic hydrocarbons (PAH), asbestos, silica, diesel exhaust fumes (DEF), chrome and paints. Test results were recorded for EGFR, KRAS, HER2, BRAF and PIK3 mutations, and ALK alterations.Overall, 313 out of 384 patients included in BioCAST were analysed. Asbestos-exposed patients displayed a significantly lower rate of EGFR mutations (20% versus 44%, p=0.033), and a higher rate of HER2 mutations (18% versus 4%, p=0.084). ALK alterations were not associated with any occupational carcinogens. The DEF-exposed patients were diagnosed with a BRAF mutation in 25% of all cases. Chrome-exposed patients exhibited enhanced HER2 and PIK3 mutation frequency.Given its minimal effects in the subgroups, we conclude that occupational exposure slightly affects the molecular pattern of lung cancers in never-smokers. In particular, asbestos-exposed patients have a lower chance of EGFR mutations.

Copyright ©ERS 2017.
Chest physician-reported, work-related, long-latency respiratory disease in Great Britain. M. Carder, A. Darnton, M. Gittins, et al. 2017;50(6). PubMed · Publisher

Abstract

Much of the current burden of long-latency respiratory disease (LLRD) in Great Britain is attributed to historical asbestos exposure. However, continuing exposure to other agents, notably silica, also contributes to disease burden. The aim of this study was to investigate the incidence of work-related LLRD reported by chest physicians in Great Britain, including variations by age, gender, occupation and suspected agent.LLRD incidence and incidence rate ratios by occupation were estimated (1996-2014). Mesothelioma cases by occupation were compared with proportional mortality ratios.Cases were predominantly in men (95%) and 92% of all cases were attributed to asbestos. Annual average incidence rates (males) per 100 000 were: benign pleural disease, 7.1 (95% CI 6.0-8.2); mesothelioma, 5.4 (4.8-6.0); pneumoconiosis, 1.9 (1.7-2.2); lung cancer, 0.8 (0.6-1.0); chronic obstructive pulmonary disease (COPD), 0.3 (0.2-0.4). Occupations with a particularly high incidence of LLRD were miners and quarrymen (COPD), plumbers and gas fitters (asbestosis), and shipyard and dock workers (all other categories). There was a clear concordance between cases of SWORD mesothelioma and proportional mortality ratios by occupation.Occupationally caused LLRD continues to contribute to a significant disease burden. Many cases are attributable to past exposure to agents such as asbestos and silica, but the potential for occupational exposures persists.

Copyright ©ERS 2017.
Correspondence regarding the article "The asbestos fibre burden in human lungs: new insights into the chrysotile debate". L.C. Oliver, F. Belpoggi, L.T. Budnik, et al. 2017;50(6). Letter · Comment PubMed · Publisher
Correspondence regarding the article "The asbestos fibre burden in human lungs: new insights into the chrysotile debate". I.S. Feder, I. Tischoff, A. Theile, et al. 2017;50(6). Letter · Comment PubMed · Publisher

Summary

In this reply, the authors of a 2017 European Respiratory Journal study of asbestos fibre burden in human lungs responded to correspondence from X. Baur and colleagues criticising that study. They stated that the debate about chrysotile causing malignant and non-malignant pleural and lung diseases was over, but that the question of chrysotile biopersistence in workers' lungs remained open. They reported that their study showed high biopersistence of chrysotile fibres in human lungs, in contrast to animal data, and said this was a strong argument for a global ban of asbestos. On concerns about compensation claims, they stated that under the Helsinki criteria a histological diagnosis of asbestosis requires fibrosis plus asbestos bodies or uncoated asbestos fibres. They said they saw no disadvantage for patients with true asbestosis. They described their work as a longitudinal observational study largely unaffected by sample size. They cited an editorial by Nemery et al. reporting seven patients with repeated bronchoalveolar lavage, and a study by Sartorelli et al. of 22 patients, as giving similar results. They stated that the lower chrysotile fraction in lungs than at workplaces reflects lower deposition and accumulation rather than long-term clearance. They maintained that conflicts of interest had been properly disclosed. They concluded that asbestos fibres, including chrysotile, are highly biopersistent in human lungs.

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Correspondence regarding the article "The asbestos fibre burden in human lungs: new insights into the chrysotile debate". P. Sartorelli. 2017;50(6). Letter · Comment PubMed · Publisher
Exhaled breath to screen for malignant pleural mesothelioma: a validation study. K. Lamote, M. Vynck, O. Thas, et al. 2017;50(6). PubMed · Publisher

Abstract

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.

Copyright ©ERS 2017.
Quantifying asbestos in lung tissue: what debate?. B. Nemery, V. Nuyts, K. Nackaerts. 2017;49(6). Editorial · Comment PubMed · Publisher
The asbestos fibre burden in human lungs: new insights into the chrysotile debate. I.S. Feder, I. Tischoff, A. Theile, et al. 2017;49(6). PubMed · Publisher · Free full text

Abstract

The traceability of asbestos fibres in human lungs is a matter of discussion especially for chrysotile. This issue is of high significance for differential diagnosis, risk assessment and occupational compensation. At present no intra-individual longitudinal information is available. This study addresses the question whether the asbestos fibre burden in human lungs decreases with time after exposure cessation.The database of the German Mesothelioma Register was screened for patients with asbestos body counts of at least 500 fibres per gram of wet lung, which had been analysed twice from different tissue excisions at minimum intervals of 4 years.Twelve datasets with individual longitudinal information were discovered with a median interval of about 8 years (range 4-21 years). Both examinations were performed after exposure cessation (median: surgery, 9.5 years; autopsy, 22 years). Pulmonary asbestos fibre burden was stable between both examinations (median 1623/4269 asbestos bodies per gram wet lung). Electron microscopy demonstrated a preponderance of chrysotile (median 80%).This study is the first to present longitudinal intra-individual data about the asbestos fibre burden in living human lungs. The high biopersistence of amphiboles, but also of chrysotile, offers mechanistic explanations for fibre toxicity, especially the long latency period of asbestos-related diseases.

Copyright ©ERS 2017.
Incidence and familial risk of pleural mesothelioma in Sweden: a national cohort study. J. Ji, J. Sundquist, K. Sundquist. 2016;48(3):873-9. PubMed · Publisher

Abstract

Familial clustering of pleural mesothelioma was reported previously, but none of the reports quantified the familial risk of mesothelioma or the association with other cancers. The contributions of shared environmental or genetic factors to the aggregation of mesothelioma were unknown.We used a number of Swedish registers, including the Swedish Multigeneration Register and the Swedish Cancer Register, to examine the familial risk of mesothelioma in offspring. Standardised incidence ratios (SIRs) were used to calculate the risk. Age standardised incidence rates of mesothelioma were calculated from the Swedish Cancer Registry.The incidence of mesothelioma reached its peak rate in 2000 and decreased thereafter. Risk of mesothelioma was significantly increased when parents or siblings were diagnosed with mesothelioma, with SIRs of 3.88 (95% CI 1.01-10.04) and 12.37 (95% CI 5.89-22.84), respectively. Mesothelioma was associated with kidney (SIR 2.13, 95% CI 1.16-3.59) and bladder cancers (SIR 2.09, 95% CI 1.32-3.14) in siblings. No association was found between spouses.Family history of mesothelioma, including both parental and sibling history, is an important risk factor for mesothelioma. Shared genetic factors may contribute to the observed familial clustering of mesothelioma, but the contribution of shared environmental factors could not be neglected. The association with kidney and bladder cancers calls for further study to explore the underlying mechanisms.

Copyright ©ERS 2016.
Co-exposure to refractory ceramic fibres and asbestos and risk of pleural mesothelioma. A. Lacourt, M. Rinaldo, C. Gramond, et al. 2014;44(3):725-33. PubMed · Publisher

Abstract

The aim of this study was to investigate the hypothesis of an increased risk of pleural mesothelioma due to co-exposure to asbestos and refractory ceramic fibres (RCF) compared to asbestos exposure alone. Males were selected from a French case-control study conducted in 1987-1993 and from the French National Mesothelioma Surveillance Program in 1998-2006. Two population controls were frequency matched to each case by year of birth. Complete job histories were collected and occupational asbestos and RCF exposures were assessed using job exposure matrices. The dose-response relationships for asbestos exposure were estimated from an unconditional logistic regression model in subjects exposed to asbestos only (group 1) and subjects exposed to both asbestos and RCF (group 2). A total of 988 cases and 1125 controls ever-exposed to asbestos were included. A dose-response relationship was observed in both groups but it was stronger in group 2. In comparison with subjects exposed at the minimum value of the cumulative index of exposure, the odds ratio was 2.6 (95% CI 1.9-3.4) for subjects exposed to 75 fibres · mL(-1) · year(-1) in group 1 increasing to 12.4 (95% CI 4.6-33.7) in group 2. Our results suggest that the pleural carcinogenic effect of occupational asbestos exposure may be modified by additional exposure to RCF.

©ERS 2014.
Multimodal management of malignant pleural mesothelioma: where are we today?. P.E. Van Schil, I. Opitz, W. Weder, et al. 2014;44(3):754-64. Editorial PubMed · Publisher

Abstract

The prognosis of patients with malignant pleural mesothelioma remains poor and although it is clear that multimodal therapy is necessary to improve long-term results, precise treatment schemes have not yet been unequivocally established. Single-modality therapy does not have a major impact on long-term survival and combined-modality therapies are being further evaluated. However, the relative contributions of chemotherapy, radiotherapy and surgery have not been clearly determined at the present time. Moreover, the extent of resection and precise surgical procedure remain a highly debated topic. To better compare and combine results from different institutions and trials, uniform definitions of surgical procedures including extrapleural pneumonectomy and different forms of pleurectomy have recently been introduced. Due to the relatively higher morbidity and mortality of extrapleural pneumonectomy, there is currently a shift towards pleurectomy/decortication when a macroscopic complete resection of all tumour can be obtained by this procedure. In most recent trials, induction chemotherapy was administered to improve surgical resection rates but pathological complete responses are infrequently observed. The role of post-operative radiotherapy has to be further elucidated. Further treatment options that are currently explored include hyperthermic intrapleural chemotherapy, immunotherapy, gene therapy and photodynamic therapy. However, no randomised comparisons are available yet.

©ERS 2014.
A prospective trial evaluating the role of mesothelin in undiagnosed pleural effusions. C.E. Hooper, A.J. Morley, P. Virgo, et al. 2013;41(1):18-24. PubMed · Publisher

Abstract

Mesothelin has been proposed as a useful tool in the diagnosis of malignant pleural mesothelioma (MPM). We aimed to examine its diagnostic utility and the impact of renal impairment on results. We prospectively recruited 230 patients with new undiagnosed pleural effusions, testing serum (n=216) and pleural fluid (n=206) mesothelin (by ELISA) during the initial consultation. 28 (12%) out of 230 patients had MPM. Serum mesothelin gave sensitivity 59.3%, specificity 64.7%, negative predictive value (NPV) 91.2%, positive predictive value (PPV) 20.5%, and pleural fluid sensitivity 72.0%, specificity 87.5%, NPV 95.5%, PPV 46.2% for distinguishing effusions due to MPM. In a matched comparison, diagnostic characteristics of pleural fluid mesothelin were superior to serum (p=0.0001). Serum mesothelin levels in patients without MPM were higher in patients with renal impairment (p=0.007) while pleural fluid levels were unaffected. 19 (54%) out of 35 patients with a benign pleural effusion and an estimated glomerular filtration rate ≤ 59 mL · min(-1) had a false-positive serum mesothelin result. The diagnostic accuracy of pleural fluid mesothelin is superior to that of serum and is unaffected by renal function. In patients with a low pre-test probability of mesothelioma, a negative mesothelin test could be reassuring, because of its high NPV. Routine use of mesothelin testing in undiagnosed pleural effusions at presentation appears to be unhelpful.
Effectiveness of mesothelin family proteins and osteopontin for malignant mesothelioma. I. Pantazopoulos, P. Boura, T. Xanthos, et al. 2013;41(3):706-15. Review PubMed · Publisher

Abstract

Malignant mesothelioma (MM) is an aggressive tumour with poor prognosis whose early diagnosis is difficult. Mesothelin, megakaryocyte potentiating factor (MPF) and osteopontin have attracted attention as biomarkers. The aim of the present review is to provide an overview regarding these candidate biomarkers for MM, and discuss their potential role in today's clinical practice. Mesothelin and MPF have good specificity but sub-optimal sensitivity for detection of MM, being negative both in the sarcomatoid histological sub-type and in almost half of epithelioid mesothelioma, especially in the early stages. Osteopontin is a marker of the duration of asbestos exposure, but lacks specificity for mesothelioma. Several patient characteristics influence the diagnostic accuracy of biomarkers and make the establishment of the "optimal" diagnostic threshold difficult. Mesothelin and MPF have proved useful in assessing response to treatment. Combining different markers together may lead to an improvement in diagnostic accuracy, but there is still need for research in this area. Extensive validation and further research is required to improve the use of serum markers in mesothelioma management. In the near future, their application in clinical practice is probably in monitoring response to therapy, rather than in guiding diagnostic decisions and risk assessment of asbestos-exposed populations.
Mesothelin and osteopontin. G. Hillerdal. 2013;42(2):557. Letter · Comment PubMed · Publisher
Mesothelin and osteopontin. I. Pantazopoulos, T. Xanthos, P. Boura, et al. 2013;42(2):557-8. Letter · Comment PubMed · Publisher
A breath test for malignant mesothelioma using an electronic nose. E.A. Chapman, P.S. Thomas, E. Stone, et al. 2012;40(2):448-54. PubMed · Publisher

Abstract

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.
Malignant mesothelioma in Metsovo, Greece, from domestic use of asbestos: 30 years later. A. Gogali, C. Manda-Stachouli, E.E. Ntzani, et al. 2012;39(1):217-9. Letter PubMed · Publisher

Summary

This research letter updated earlier reports on malignant mesothelioma (MM) in Metsovo, a group of villages in Ioannina prefecture, north-west Greece. Earlier work linked MM there to a tremolite asbestos-containing whitewash called 'luto', which was gradually abandoned after 1940–1950 and no longer used by 1990. The authors asked whether, 30 years after the first recorded case, the epidemic was ending. The populations of Metsovo municipality (4,417 inhabitants in 2001) and Ioannina prefecture were followed from January 1980 to December 2009, giving 127,753 and 4,733,915 person-years respectively. Cases were identified through the registries of two tertiary hospitals in Ioannina and the Metsovo death certificate registry. All were histologically confirmed, and none had an asbestos-related occupation. Crude incidence rates were calculated because age data were unavailable. There were 26 MM cases in Metsovo, a rate of 2.04 per 10,000 person-years. Of these, 14 occurred in 1980–1994 and 12 in 1995–2009. The rates for these two 15-year periods were 2.2 and 1.8 per 10,000 person-years (p=0.65). By decade, rates were 2.6, 2.4 and 1.1 per 10,000 person-years (p=0.1 for the last decade versus the previous one). Compared with the rest of Ioannina (1.48 per 1,000,000 person-years), risk in Metsovo was 137-fold higher, falling from 236-fold to 86-fold between the two 15-year periods. The authors concluded that incidence had dropped by half and relative risk by two-thirds, but that no prediction of the epidemic's end was safe.

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In plain English

This research letter updated the authors' earlier reports on malignant mesothelioma in Metsovo, north-west Greece. Households there had used 'luto', a whitewash containing tremolite asbestos. The team followed the Metsovo municipality population (4,417 inhabitants in 2001) and the rest of Ioannina prefecture from 1980 to 2009. None of the patients had an asbestos-related job. Metsovo had 26 cases, a crude rate of 2.04 per 10,000 person-years. Twelve occurred in 1995–2009 (10 pleural, two peritoneal), all in people who had used luto in 1950–1970. The 1995–2009 rate (1.8 per 10,000 person-years) was not statistically different from the 1980–1994 rate (2.2). The last decade's rate (1.1 per 10,000 person-years) was less than half the previous decade's (2.4; p=0.1), which the authors called a trend. Metsovo residents had an estimated 137-fold higher risk than the rest of Ioannina (95% CI 58.2–375.6). This fell from 236-fold in the first 15 years to 86-fold in the second. The authors concluded that abandoning luto had cut incidence to one-half and relative risk to one-third, and that the epidemic may still end by 2020–2030, though no prediction is safe. Rates were not age-adjusted.

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Mesothelioma incidence projections in South East England. S.P. Riaz, V.H. Coupland, M. Lüchtenborg, et al. 2012;40(4):965-8. PubMed · Publisher

Abstract

We estimated the past and future age-standardised incidence rates of mesothelioma by birth cohort and by period of diagnosis in South East England. We extracted data on patients diagnosed with mesothelioma (International Classification of Diseases-10 C45) between 1960 and 2009 from the Thames Cancer Registry. We calculated the age-standardised incidence rates using the European standard population. We used age-cohort and age-period modelling to estimate the age-specific incidence rates for the 1900 to 1950 birth cohorts and the 1935 to 2034 calendar periods. A much more pronounced increase in mesothelioma incidence between 1972 and 2007 was observed in males than in females. In both sexes, the incidence rates increased in successive generations up to the 1945 birth cohort. Projection of rates in the future showed an increase in incidence in males until 2022 and a decrease thereafter. Among females, the incidence rate was predicted to increase gradually until reaching its maximum around 2027, and to remain stable thereafter. The occurrence of mesothelioma is closely linked to occupational exposure to asbestos in the 1960s and 1970s and, due to the long latency period, the incidence of mesothelioma is projected to increase until the 2020s.
Population-based survival for malignant mesothelioma after introduction of novel chemotherapy. R.A. Damhuis, C. Schroten, J.A. Burgers. 2012;40(1):185-9. PubMed · Publisher

Abstract

Malignant mesothelioma is known for its dismal prognosis and poor response to conventional treatment. Chemotherapy with cisplatin-antifolate combinations recently showed promising response rates and prolonged survival in randomised trials. To assess the impact of this development on clinical practice and survival at a population-based level, treatment patterns and survival trends were studied for patients diagnosed with mesothelioma in the period 1995-2006. 4,731 records were retrieved from the Netherlands Cancer Registry and chemotherapy use and median survival were analysed. For the periods 1995-1998 to 2005-2006, chemotherapy use increased from 8% to 36%. Median survival increased over time from 7.1 months to 9.2 months. For pleural mesothelioma, multivariable analysis demonstrated that survival was poorer for elderly patients and sarcomatoid tumours. The prognostic impact of chemotherapy increased with time. Median survival for chemotherapy treated patients improved from 10.1 months (1995-1998) to 13.1 months (2005-2006). For peritoneal mesothelioma, median survival was poor (3.9 months) but better for females and younger patients. This study demonstrates that chemotherapy use increased at a national level and coincided with an improvement in survival. The novel chemotherapy regimen appears to be more effective but, due to the observational nature of this study, alternative explanations cannot be excluded.
Predicting survival in malignant mesothelioma. J.G. Smith. 2012;40(3):799. Letter · Comment PubMed · Publisher
Predicting survival in mesothelioma. A.W. Musk. 2012;40(6):1582. Letter · Comment PubMed · Publisher
Temporal patterns of occupational asbestos exposure and risk of pleural mesothelioma. A. Lacourt, K. Leffondré, C. Gramond, et al. 2012;39(6):1304-12. PubMed · Publisher

Abstract

Asbestos is the primary cause of pleural mesothelioma (PM). The objective of this study was to elucidate the importance of different temporal patterns of occupational asbestos exposure on the risk of PM using case-control data in male subjects. Cases were selected from a French case-control study conducted in 1987-1993 and the French National Mesothelioma Surveillance Program in 1998-2006. Population controls were frequency matched to cases by year of birth. Occupational asbestos exposure was evaluated with a job-exposure matrix. The dose-response relationships were estimated using restricted cubic spline functions in logistic regression models. A total of 2,466 ever-asbestos-exposed males (1,041 cases and 1,425 controls) were used. After adjustment for intensity and total duration of occupational asbestos exposure, the risk of PM was lower for subjects first exposed after the age of 20 yrs and continued to increase until 30 yrs after cessation of exposure. The effect of total duration of exposure decreased when age at first exposure and time since last exposure increased. These results, based on a large population-based case-control study, underline the need to take into account the temporal pattern of exposure on risk assessment.
A 5-aza-2'-deoxycytidine/valproate combination induces cytotoxic T-cell response against mesothelioma. S. Leclercq, F. Gueugnon, B. Boutin, et al. 2011;38(5):1105-16. PubMed · Publisher

Abstract

Malignant pleural mesothelioma (MPM) is an aggressive tumour with a limited response to conventional therapy. The aim of this study was to evaluate the anticancer effect of a DNA methyltransferase inhibitor, 5-aza-2'-deoxycytidine (5-azaCdR), and two histone deacetylase inhibitors, valproic acid (VPA) and suberoylanilide hydroxamic acid (SAHA). Human mesothelioma cells were treated with each epigenetic drug, either alone or in combinations. The cytotoxic effects on treated cells and the expression of specific tumour antigens were evaluated. The recognition of treated cells by a specific CD8+ T-cell clone was also measured. Additionally, the effect of combined treatments was tested in a murine model of mesothelioma. We showed that VPA and SAHA synergised with 5-azaCdR to kill MPM cells and induce tumour antigen expression in the remaining living tumour cells. As a consequence, tumour cells expressing these antigens were recognised and lysed by specific CD8+ cytotoxic T-cells. In vivo, treatment with 5-azaCdR/VPA inhibited tumour growth, and promoted lymphocyte infiltration and an immune response against tumour cells. Appropriate epigenetic drug combinations, in addition to inducing mesothelioma cell death, also affect the immunogenic status of these cells. This property could be exploited in clinical investigations to develop MPM treatments combining chemotherapeutic and immunotherapeutic approaches.
Genetic susceptibility to asbestos-related fibrotic pleuropulmonary changes. M.K. Kukkonen, S. Hämäläinen, S. Kaleva, et al. 2011;38(3):672-8. PubMed · Publisher

Abstract

The objective of this study was to determine whether genetic polymorphisms in enzymes that metabolise oxidative agents modify the individual susceptibility to developing asbestos and smoking-related pleuropulmonary changes. Nine polymorphisms of six genes (EPHX1, GSTM1, GSTM3, GSTP1, GSTT1 and NAT2) were genotyped from 1,008 Finnish asbestos-exposed workers. The genotype data were compared to signs of lung fibrosis and pleural thickenings, as well as with total lung capacity, single-breath diffusing capacity of the lung for carbon monoxide (D(L,CO)) and specific diffusing capacity (expressed as D(L,CO) per unit of alveolar volume (V(A))). The GSTT1 deletion polymorphism was associated with fibrotic changes (p=0.003), and decreased D(L,CO) (p=0.02) and D(L,CO)/V(A) (p=0.002), and the GSTM1 deletion polymorphism was associated with the greatest thickness of pleural plaques (p=0.009). On further analysis, the GSTT1 null genotype was found to pose over a three-fold risk for severe fibrotic changes (OR 3.12, 95% CI 1.51-6.43), and around two-fold risks for decreased D(L,CO) (OR 1.77, 95% CI 1.06-2.95) and D(L,CO)/V(A) (OR 2.37, 95% CI 1.33-4.23). In addition, the GSTM1 null genotype showed an elevated risk (OR 1.36, 95% CI 1.03-1.80) for thicker pleural plaques. Our data suggest that inherited detoxification capacity may affect the development and severity of asbestos and smoking-related nonmalignant pulmonary changes.
Lung function, radiological changes and exposure: analysis of ATSDR data from Libby, MT, USA. D. Weill, G. Dhillon, L. Freyder, et al. 2011;38(2):376-83. PubMed · Publisher

Abstract

In 2000, the Agency for Toxic Substances and Disease Registry (ATSDR; Atlanta, GA, USA) investigated lung disease in those exposed to the tremolite-contaminated vermiculite mine in Libby, MT, USA. Previously unreported spirometric results are presented here in relation to exposure and radiographic findings. 4,524 study participants were assigned to one of seven mutually exclusive exposure categories. Associations among radiographic findings, spirometric results and exposure were investigated, along with the effect of a reduction in exposure potential when production was moved to a wet process mill in the mid 1970s. Spirometry data for the total population by smoking status and age were within the normal range. Prevalence of pleural plaque increased with age, but was lowest in the environmentally exposed group (0.42-12.74%) and greatest in the W.R. Grace & Co. mineworkers (20-45.68%). For males, there was a significant (4.5%) effect of pleural plaques on forced vital capacity. For W.R. Grace & Co. workers and household contacts, a reduction in plaque (0.11 versus 1.64%) and in diffuse pleural thickening or costophrenic angle obliteration (1.94 and 0.13%) was noted for those exposed after 1976. These analyses do not support a clinically important reduction in spirometry of this cohort. The 1976 reductions in exposure have led to decrease in radiographic changes.
Predicting survival in malignant mesothelioma. A.W. Musk, N. Olsen, H. Alfonso, et al. 2011;38(6):1420-4. PubMed · Publisher

Abstract

Malignant mesothelioma (MM) of the pleura or peritoneum is a universally fatal disease attracting an increasing range of medical interventions and escalating healthcare costs. Changes in survival and the factors affecting survival of all patients ever diagnosed with MM in Western Australia over the past five decades and confirmed by the Western Australian Mesothelioma Registry to December 2005 were examined. Sex, age, date and method of diagnosis, site of disease and histological type were recorded. Date of onset of symptoms and performance status were obtained from clinical notes for a sample of cases. Cox regression was used to examine the association of the clinical variables and the 10-yr periods of disease onset with survival after diagnosis. Survival was inversely related to age, being worse for males (hazard ratio (HR) 1.4, 95% CI 1.2-1.6), and those with peritoneal mesothelioma (HR 1.4, 95% CI 1.1-1.7). Patients with sarcomatoid histology had worse prognosis than patients with epithelioid and biphasic histological subtypes. Survival improved after the 1970s and has made incremental improvements since then. Median (interquartile range) survival by decade, from 1960 until 2005, was 64 (0-198), 177 (48-350), 221 (97-504), 238 (108-502) and 301 (134-611) days; ~4 weeks of this apparent improvement can be attributed to earlier diagnosis. With increasing resources and treatment costs for MM over the past 40 yrs, there have been modest improvements in survival but no complete remissions.
Recognition of pleural mesothelioma by mucin-1(950-958)/human leukocyte antigen A*0201-specific CD8+ T-cells. D. Roulois, V. Vignard, F. Gueugnon, et al. 2011;38(5):1117-26. PubMed · Publisher

Abstract

Recent clinical investigations have demonstrated that T-cell-based immunotherapy of malignant pleural mesothelioma (MPM) could represent an alternative to the other therapeutic strategies. However, its development suffers from the lack of identified tumour antigenic targets. Mucin (MUC)1, which is expressed and recognised by cytotoxic T-cells in numerous cancer types, has not been investigated as a potential immune target in MPM. Thus, the objective of this study was to analyse MUC1 expression by MPM cells and to determine whether this antigen can be the target of cytotoxic CD8+ T-cells (cytotoxic T-lymphocytes (CTLs)). We first evaluated the expression and glycosylation of MUC1 by MPM cell lines using different MUC1-specific monoclonal antibodies. We then obtained a CTL clone specific for a MUC1 peptide (residues 950-958) presented by human leukocyte antigen (HLA)-A*0201 and studied its interferon-γ and cytotoxic response to MPM cell lines. We found that all MPM cell lines expressed MUC1 protein at the cell surface with different glycosylation profiles. We also observed that HLA-A*0201+ MPM cell lines are recognised and lysed by a HLA-A*0201/MUC1(950-958)-specific CTL clone independently of the MUC1 glycosylation profile. Thus, MUC1 expression and antigen presentation by MPM cells may represent an attractive target for immunotherapeutic treatment of MPM despite its hyperglycosylated profile.
Respiratory illness in asbestos contaminated sites: the role of environmental exposure. P. Comba, L. Fazzo, A. Zona. 2011;38(2):248-50. Comment · Editorial PubMed · Publisher

Summary

This editorial commented on a study by Weill et al., published in the same issue of the European Respiratory Journal, of lung function and radiological changes in relation to exposure to tremolite-contaminated vermiculite in Libby, Montana, USA. The authors first summarised literature on environmental asbestos exposure, including tremolite-related mesothelioma and pleural plaques from soil contamination in several countries, and studies of Libby workers, household contacts and residents. Weill et al. had used data from a 2000 survey of 7,307 current or former residents by the Agency for Toxic Substances and Disease Registry (ATSDR). They restricted the analysis to 4,524 subjects aged 25-90 years who had no asbestos exposure other than through vermiculite. They reported that pleural plaques increased with age and were less common with environmental than occupational exposure. Plaques had a significant effect on forced vital capacity in males. Pleural abnormalities were less prevalent in the general population exposed after 1976. The editorial authors argued that exposure categories should consider distance from fibre sources and duration of residence. They said mesothelioma data were available, citing nine Libby cases diagnosed between 1993 and 2006 that were associated with environmental exposure. They also noted the lack of carbon monoxide diffusion testing, and that ATSDR had found moderate-to-severe restriction in 1.8% of those tested. They concluded that the findings supported reduced risk after 1976 mitigation but could not rule out adverse respiratory effects. They suggested that pleural mesothelioma monitoring might be informative.

PubMed has no abstract for this study, and the article doesn't print one. We wrote this summary from the full article with the help of AI. It is not the authors' wording.
Valproate-doxorubicin: promising therapy for progressing mesothelioma. A phase II study. A. Scherpereel, T. Berghmans, J.J. Lafitte, et al. 2011;37(1):129-35. PubMed · Publisher

Abstract

No treatment is recommended for patients with malignant mesothelioma (MM) failing after first-line cisplatin-based chemotherapy. In vitro data suggested that valproic acid, a histone deacetylase inhibitor (HDACi), had a proapoptotic effect and synergised with doxorubicin to induce apoptosis in MM cells. Our primary end-point was to determine response rate of combined valproic acid and doxorubicin in patients with unresectable MM failing after platinum-based chemotherapy. Treatment consisted of doxorubicin (60 mg·m⁻²) plus valproic acid. An interim analysis for response rate was planned after the first 16 registered patients. All the cases were centrally reviewed. From July 2006 to March 2009, 45 eligible patients with pleural MM were registered. The majority of the patients were male (73%), had a performance status (PS) ≥ 80 (76%) and an epithelioid subtype (80%). There were seven partial responses (response rate 16%; 95% CI 3-25%), all in patients with PS 80-100. The best disease control rate was 36% (95% CI 22-51%). Two toxic deaths were observed (febrile neutropenia and cerebral thrombotic event), both in patients with poor PS (60-70). Valproic acid, an HDACi, plus doxorubicin appeared an effective chemotherapy regimen in good PS (80-100) patients with refractory or recurrent MM, for which no standard therapy was available.
Volumetry: an alternative to assess therapy response for malignant pleural mesothelioma?. T. Frauenfelder, M. Tutic, W. Weder, et al. 2011;38(1):162-8. PubMed · Publisher

Abstract

The purpose of our study was to assess robustness of volumetric measurement of malignant pleural mesothelioma (MPM) before and after chemotherapy to modified RECIST (response evaluation criteria in solid tumours) criteria. 30 patients with digitally available chest computed tomography (CT) scans before and after three cycles of chemotherapy were included. Three readers independently assessed tumour response using two different methods: 1) the modified RECIST criteria; and 2) the tumour volumetric approach using dedicated software (Myrian; Intrasense, Paris, France). Inter-rater reliability of unidimensional and volumetric measurements was assessed using intraclass correlation. Tumour response classification for modified RECIST was compared to the volumetric approach applying unidimensional RECIST volumetric equivalent criteria. The determination of unidimensional tumour measurement (RECIST) revealed a low inter-rater reliability (0.55) and a low interobserver agreement for tumour response classification (general κ 0.33). Only 14 patients were classified equally. A high inter-rater reliability (0.99) and interobserver agreement (general κ 0.9) were found for absolute tumour volumes (volumetric measurements). 27 cases were classified equally. The number of cases classified as "stable disease" was higher for the volumetric approach using tumour-equivalent criteria compared to modified RECIST. Volumetric measurement of MPM on CT using Myrian software is a reliable, reproducible and sensitive method to measure tumour volume and, thus, therapy response after induction chemotherapy.
A novel clinical role for angiopoietin-1 in malignant pleural mesothelioma. C. Tabata, N. Hirayama, R. Tabata, et al. 2010;36(5):1099-105. PubMed · Publisher

Abstract

Malignant pleural mesothelioma (MPM) is an aggressive malignant tumour associated with asbestos exposure that has only a limited response to conventional therapy; therefore, diagnosing MPM early is very important. We have previously reported that angiopoietin (Ang)-1 was correlated with bleomycin-induced pulmonary fibrosis. Here, we investigated the association of Ang-1 with the development of MPM cells, which originate from mesenchymal cells similar to lung fibroblasts, and demonstrated that Ang-1 stimulated the growth and migration of MPM cells in vitro. We also demonstrated that patients with MPM had significantly higher serum levels of Ang-1 in comparison to a population who had been exposed to asbestos but had not developed MPM. The patients with advanced-stage MPM showed higher levels of Ang-1 than the early-stage MPM patients and the Kaplan-Meier method revealed a significant correlation between serum Ang-1 levels and survival. We propose the possibility that Ang-1 plays an important role in MPM tumour growth and our data suggest that the serum concentration of Ang-1 could be useful as prognostic factor.
Current data on predictive markers for anti-angiogenic therapy in thoracic tumours. N. Reinmuth, M. Thomas, M. Meister, et al. 2010;36(4):915-24. Review PubMed · Publisher

Abstract

The fact that growth and spread of tumours are dependent on angiogenesis has led to the investigation of the role of anti-angiogenic agents in the therapeutic strategies for thoracic tumours such as nonsmall cell lung cancer or mesotheliomas. Since various angiogenic factors may contribute to the regulation of angiogenesis in the individual tumour, in the era of increasing amounts of clinically tested agents it is of utmost importance to properly select patients that may benefit from a specific therapy. Due to the complex nature of tumour angiogenesis, various biomarkers may be applicable. For example, the profile of activated angiogenic pathways in endothelial cells may be determined in order to make conclusions about the relevance of inhibiting a given pathway by a selected agent. Moreover, changes in protein expression in stromal and tumour cells, as well as structural alterations in the vasculature, may be used for predicting and monitoring the clinical effects of such a therapy. In this review, the current data from clinical studies evaluating predictive markers for anti-angiogenic agents in thoracic cancers are summarised. Besides giving clinical examples, the rationales for investigating various parameters based on pre-clinical studies are described.
Guidelines of the European Respiratory Society and the European Society of Thoracic Surgeons for the management of malignant pleural mesothelioma. A. Scherpereel, P. Astoul, P. Baas, et al. 2010;35(3):479-95. Guideline PubMed · Publisher

Abstract

Malignant pleural mesothelioma (MPM) is a rare tumour but with increasing incidence and a poor prognosis. In 2008, the European Respiratory Society/European Society of Thoracic Surgeons Task Force brought together experts to propose practical and up-to-dated guidelines on the management of MPM. To obtain an earlier and reliable diagnosis of MPM, the experts recommend performing thoracoscopy, except in cases of pre-operative contraindication or pleural symphysis. The standard staining procedures are insufficient in approximately 10% of cases. Therefore, we propose using specific immunohistochemistry markers on pleural biopsies. In the absence of a uniform, robust and validated staging system, we advice use of the most recent TNM based classification, and propose a three step pre-treatment assessment. Patient's performance status and histological subtype are currently the only prognostic factors of clinical importance in the management of MPM. Other potential parameters should be recorded at baseline and reported in clinical trials. MPM exhibits a high resistance to chemotherapy and only a few patients are candidates for radical surgery. New therapies and strategies have been reviewed. Because of limited data on the best combination treatment, we emphasise that patients who are considered candidates for a multimodal approach should be included in a prospective trial at a specialised centre.
Trimodality therapy for malignant pleural mesothelioma: results from an EORTC phase II multicentre trial. P.E. Van Schil, P. Baas, R. Gaafar, et al. 2010;36(6):1362-9. PubMed · Publisher

Abstract

The European Organisation for Research and Treatment of Cancer (EORTC; protocol 08031) phase II trial investigated the feasibility of trimodality therapy consisting of induction chemotherapy followed by extrapleural pneumonectomy and post-operative radiotherapy in patients with malignant pleural mesothelioma (with a severity of cT3N1M0 or less). Induction chemotherapy consisted of three courses of cisplatin 75 mg·m⁻² and pemetrexed 500 mg·m⁻². Nonprogressing patients underwent extrapleural pneumonectomy followed by post-operative radiotherapy (54 Gy, 30 fractions). Our primary end-point was "success of treatment" and our secondary end-points were toxicity, and overall and progression-free survival. 59 patients were registered, one of whom was ineligible. Subjects' median age was 57 yrs. The subjects' TNM scores were as follows: cT1, T2 and T3, 36, 16 and six patients, respectively; cN0 and N1, 57 and one patient, respectively. 55 (93%) patients received three cycles of chemotherapy with only mild toxicity. 46 (79%) patients received surgery and 42 (74%) had extrapleural pneumonectomy with a 90-day mortality of 6.5%. Post-operative radiotherapy was completed in 37 (65%) patients. Grade 3-4 toxicity persisted after 90 days in three (5.3%) patients. Median overall survival time was 18.4 months (95% CI 15.6-32.9) and median progression-free survival was 13.9 months (95% CI 10.9-17.2). Only 24 (42%) patients met the definition of success (one-sided 90% CI 0.36-1.00). Although feasible, trimodality therapy in patients with mesothelioma was not completed within the strictly defined timelines of this protocol and adjustments are necessary.

2000s

All-trans-retinoic acid inhibits tumour growth of malignant pleural mesothelioma in mice. C. Tabata, R. Tabata, N. Hirayama, et al. 2009;34(5):1159-67. PubMed · Publisher

Abstract

Malignant pleural mesothelioma (MPM) is an aggressive malignant tumour of mesothelial origin associated with asbestos exposure. Because MPM has limited response to conventional chemotherapy and radiotherapy, the prognosis is very poor. Several researchers have reported that cytokines such as interleukin (IL)-6 play an important role in the growth of MPM. Previously, it was reported that all-trans-retinoic acid (ATRA) inhibited the production and function of IL-6 and transforming growth factor (TGF)-beta1 in experiments using lung fibroblasts. We investigated whether ATRA had an inhibitory effect on the cell growth of MPM, the origin of which was mesenchymal cells similar to lung fibroblasts, using a subcutaneous xenograft mouse model. We estimated the tumour growth and performed quantitative measurements of IL-6, TGF-beta1 and platelet-derived growth factor (PDGF) receptor (PDGFR)-beta mRNA levels both of cultured MPM cells and cells grown in mice with or without the administration of ATRA. ATRA significantly inhibited MPM tumour growth. In vitro studies disclosed that the administration of ATRA reduced 1) mRNA levels of TGF-beta1, TGF-beta1 receptors and PDGFR-beta, and 2) TGF-beta1-dependent proliferation and PDGF-BB-dependent migration of MPM cells. These data may provide a rationale to explore the clinical use of ATRA for the treatment of MPM.
Local effector failure in mesothelioma is not mediated by CD4+ CD25+ T-regulator cells. C. Jackaman, S. Cornwall, A.M. Lew, et al. 2009;34(1):162-75. PubMed · Publisher

Abstract

The aim of the present study was to define the point at which mesothelioma T-cell responses fail in order to design better immunotherapies. A murine model of mesothelioma was used which was established with asbestos. Inoculation of tumour cells into syngeneic mice results in progressing tumours with similar histopathology to human mesothelioma. The tumour cells secrete a marker tumour antigen similar to secreted tumour-associated products, such as mesothelin. The mesothelioma microenvironment contains stromal elements including dendritic cells, effector CD8(+) and CD4(+) T-cells, and CD4(+) T-regulatory (Tregs) cells, all of which are activated in situ, implying chronic inflammation. Tumour antigens are rapidly transported to draining lymph nodes wherein tumour-specific T-cell responses are generated. Despite the generation of potent CD8(+) cytotoxic lymphocyte in lymphoid organs, those that infiltrate tumours cannot restrain tumour growth suggesting local suppression. Splenic Tregs did not suppress protective responses in adoptive transfer experiments suggesting that systemic Tregs play little role in regulating anti-mesothelioma immune responses. Finally, removal of CD25(+) Tregs from the tumour site and lymphoid organs did not alter tumour growth with or without interleukin (IL)-2 or IL-21 immunotherapy. Tregs are not potent regulators of anti-mesothelioma immunity and targeting these cells may not improve results.
Pleural plaques and asbestosis: dose- and time-response relationships based on HRCT data. C. Paris, S. Thierry, P. Brochard, et al. 2009;34(1):72-9. PubMed · Publisher

Abstract

Most studies on asbestos-related diseases are based on chest radiographs, and dose-response relationships are still controversial. The aim of this study was to describe the most relevant parameters of asbestos exposure linked to pleural plaques and asbestosis diagnosed by high-resolution computed tomography (HRCT). A large screening programme including systematic HRCT examinations was organised from 2003 to 2005 in France for formerly asbestos-exposed workers. The time since first exposure (TSFE), level, duration and cumulative exposure to asbestos were used in adjusted unconditional logistic regression to model the relationships of the two diseases. Analysis of a population of 5,545 subjects demonstrated that TSFE (p<0.0001) and cumulative exposure (p = 0.02) (or level, depending on the models used), were independently associated with the frequency of pleural plaques. Only cumulative exposure (p<0.0001) or level of exposure (p = 0.02) were significantly associated with asbestosis. All trend tests were significant for these parameters. To date and to our knowledge, this study is the largest programme based on HRCT for the screening of asbestos-exposed subjects. Both time-response and dose-response relationships were demonstrated for pleural plaques, while only dose-response relationships were demonstrated for asbestosis. These parameters must be included in the definition of high-risk populations for HRCT-based screening programmes.
Taurolidine and oxidative stress: a rationale for local treatment of mesothelioma. N. Aceto, P. Bertino, D. Barbone, et al. 2009;34(6):1399-407. PubMed · Publisher

Abstract

Malignant mesothelioma is an asbestos-related, aggressive tumour, resistant to most anticancer therapies. Akt is a key mediator of mesothelioma cell survival and chemoresistance. This study aimed to clarify the mechanism by which taurolidine (TN), a known synthetic compound with antimicrobial and antineoplastic properties, leads to mesothelioma cell death. Apoptosis was studied by annexin V binding, cell cycle analysis, caspase-8 activation, poly(ADP-ribose) polymerase (PARP) cleavage and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labelling (TUNEL). Oxidative stress was measured by nitrite production and DNA oxidative damage. Protein expression and phosphorylation were evaluated by immunoprecipitation and immunoblotting. TN induces cell death of mesothelioma cells, but not of non-neoplastic human mesothelial cells. After TN treatment of mesothelioma cells, Akt but not extracellular signal-regulated kinase (Erk) 1/2 activity is inhibited a in time- and dose-dependent manner. Protein phosphatase (PP)1alpha and PP2A are activated several hours after drug addition. Apoptosis induced by TN is driven by oxidative stress and cell exposure to sulfydryl donors, such as glutathione monoethylester and l-N-acetylcysteine, significantly reduced pro-apoptotic effects and Akt inhibition. Conversely, expression of constitutively activated Akt did not affect cytoxicity elicited by TN, which retained its ability to inhibit the kinase. TN induces mesothelioma cell death via oxidative stress, accompanied by inhibition of Akt signalling. This provides a promising molecular rationale for TN as local treatment of malignant mesothelioma.
Asbestos induces doxorubicin resistance in MM98 mesothelioma cells via HIF-1alpha. C. Riganti, S. Doublier, E. Aldieri, et al. 2008;32(2):443-51. PubMed · Publisher

Abstract

Human malignant mesothelioma (HMM), which is strongly related to asbestos exposure, exhibits high resistance to many anticancer drugs. Asbestos fibre deposition in the lung may cause hypoxia and iron chelation at the fibre surface. Hypoxia-inducible factor (HIF)-1alpha, which is upregulated by a decreased availability of oxygen and iron, controls the expression of membrane transporters, such as P-glycoprotein (Pgp), which actively extrude the anticancer drugs. The present study aimed to assess whether asbestos may play a role in the induction of doxorubicin resistance in HMM cells through the activation of HIF-1alpha and an increased expression of Pgp. After 24-h incubation with crocidolite asbestos or with the iron chelator dexrazoxane, or under hypoxia, HMM cells were tested for HIF-1alpha activation, Pgp expression, accumulation of doxorubicin and sensitivity to its toxic effect. Crocidolite, dexrazoxane and hypoxia caused HIF-1alpha activation, Pgp overexpression and increased resistance to doxorubicin accumulation and toxicity. These effects were prevented by the co-incubation with the cell-permeating iron salt ferric nitrilotriacetate, which caused an increase of intracellular iron bioavailability, measured as increased activity of the iron regulatory protein-1. Crocidolite, dexrazoxane and hypoxia induce doxorubicin resistance in human malignant mesothelioma cells by increasing hypoxia-inducible factor-1alpha activity, through an iron-sensitive mechanism.
Chest CT screening of asbestos-exposed workers: lung lesions and incidental findings. T. Vierikko, R. Järvenpää, T. Autti, et al. 2007;29(1):78-84. PubMed · Publisher

Abstract

The objective of the present study is to determine the feasibility of chest computed tomography (CT) in screening for lung cancer among asbestos-exposed workers. In total, 633 workers were included in the present study and were examined with chest radiography and high-resolution CT (HRCT). A total of 180 current and ex-smokers (cessation within the previous 10 yrs) were also screened with spiral CT. Noncalcified lung nodules were considered positive findings. The incidental CT findings not related to asbestos exposure were registered and further examined when needed. Noncalcified lung nodules were detected in 86 workers. Five histologically confirmed lung cancers were found. Only one of the five cancers was also detected by plain chest radiography and three were from the group of patients with a pre-estimated lower cancer probability. Two lung cancers were stage Ia and were radically operated. In total, 277 individuals presented 343 incidental findings of which 46 required further examination. Four of these were regarded as clinically important. In conclusion, computed tomography and high-resolution computed tomography proved to be superior to plain radiography in detecting lung cancer in asbestos-exposed workers with many confounding chest findings. The numerous incidental findings are a major concern for future screenings, which should be considered for asbestos-exposed ex-smokers and current smokers.
Factors determining early adherence to a lung cancer screening protocol. U. Montes, L.M. Seijo, A. Campo, et al. 2007;30(3):532-7. PubMed · Publisher

Abstract

Lung cancer screening using computed tomography (CT) is effective in detecting early stage disease. However, concerns regarding adherence have been raised. The current authors conducted a retrospective observational study of 641 asymptomatic smokers enrolled in a lung cancer screening programme between 2000 and 2003. Adherent subjects were compared with nonadherent subjects with regard to lung function, sex, age, motivation for enrollment, smoking status, distance to the referral centre, family history of lung cancer, asbestos exposure, education, the presence and type of nodule(s) seen on initial CT, and exposure to a nursing intervention designed to improve adherence. Overall, early adherence to the study protocol was 65%. Multivariate analysis confirmed the importance of sex, proximity to the referral centre, the presence of noncalcified nodules, and the nursing intervention as factors conditioning adherence to the study protocol. Patients encouraged to participate in the study were more adherent, as were former smokers. Sex interactions were observed in multivariate analysis. The nursing intervention was significant for females, while abnormal lung function improved male adherence. Adherence to lung cancer screening is particularly good among females and subjects living near the referral centre. The present study suggests the need to develop new strategies, especially those targeting males and subjects with low risk perception, in order to improve adherence.
Screening for lung cancer in a high-risk group: but I still haven't found what I'm looking for. G.A. Silvestri. 2007;29(1):6-7. Comment · Editorial PubMed · Publisher

Summary

This editorial discussed whether lung cancer screening with low-dose computed tomography (CT) was justified. It was prompted by a study in the same journal issue by Vierikko et al., who used CT to screen asbestos-exposed workers. The author reviewed the background. Randomised trials of chest radiography screening in the 1970s and 1980s detected more early-stage cancers but did not reduce lung cancer mortality, possibly because of lead, length and overdiagnosis bias. The International Early Lung Cancer Action Project had reported an estimated 88–92% 10-year survival in 412 resected stage I patients whose cancers were found by screening. However, mortality modelling studies did not appear favourable, and cost-effectiveness estimates had varied widely. The author stated that individual lung cancer risk is affected by age, smoking history, sex, airflow obstruction and asbestos exposure, so screening an "ultra high-risk" group might improve results. In the Vierikko study of asbestos-exposed persons, some of whom smoked, benign nodules (14%) far outnumbered malignant ones (0.8%). Four patients had unnecessary thoracotomies, and 44% had incidental findings. The author found it surprising that more cancers were not detected. There was no statistical difference in age, asbestos exposure or smoking history between the five subjects with cancer and the rest of the group. The author concluded that many questions would remain unanswered until results of the randomised CT screening trials were available.

PubMed has no abstract for this study, and the article doesn't print one. We wrote this summary from the full article with the help of AI. It is not the authors' wording.
Nonmalignant pleural lesions due to environmental exposure to asbestos: a field-based, cross-sectional study. M. Metintas, S. Metintas, G. Hillerdal, et al. 2005;26(5):875-80. PubMed · Publisher

Abstract

The aim of the present study was to investigate the frequencies of asbestos-related benign pleural diseases in villagers environmentally exposed to asbestos and the factors affecting these frequencies. A field-based, cross-sectional study was designed. In total, 991 villagers from 10 villages, randomly chosen from 67 villages with known use of asbestos-containing white soil in central Anatolia (Turkey), were investigated. The type of asbestos in the white soil was determined for each village, as well as air-borne fibre concentrations. The villagers were investigated with small-size chest roentgenograms and epidemiological features were recorded. The air-borne fibre levels were generally low. Despite this, pleural plaques were found in 14.4% of the villagers, 10.4% had diffuse pleural fibrosis and 0.4% asbestosis. The significant variables for plaques were age, sex, type of asbestos fibre, e.g. actinolite and tremolite, and exposure duration, while there was a negative relationship with cumulative exposure. The variables affecting diffuse pleural fibrosis were age, exposure duration and cumulative exposure. In conclusion, villagers exposed to environmental asbestos have high frequencies of pleural plaques and diffuse pleural fibrosis, similar to occupationally exposed asbestos cohorts. Different types of asbestos appear to result in different frequencies of pleural lesions.
Assessment of 18F-fluorodeoxyglucose dual-head gamma camera in asbestos lung diseases. B. Melloni, J. Monteil, F. Vincent, et al. 2004;24(5):814-21. PubMed · Publisher

Abstract

The purpose of this study was to evaluate the performance of 18F-fluorodeoxyglucose (18FDG) imaging via coincidence detection emission tomography (CDET) in identifying malignant lesions in subjects exposed to asbestos. A total of 30 patients exposed to asbestos underwent 18FDG-CDET between January 2000 and June 2003. A CDET scan of the thorax and abdomen was performed 60 min after injection of 18FDG in fasting patients, and results were obtained in slices in three axes. The CDET results were compared to those from computed tomography (CT), and pleural or surgical biopsy in patients with positive 18FDG-CDET results. All primary malignant mesotheliomas accumulated 18FDG (n=6), and, in two patients, CDET findings were superior to those of CT, allowing early detection. In two cases, lung carcinomas with malignant pleural effusion were also detected. There were five false positive CDET results: three unilateral pleural thickening, one rounded atelectasis, and one benign lung nodule. All patients with pleural plaques showed no significant 18FDG uptake. Malignant diseases were detected by 18FDG-CDET imaging with a sensitivity of 89% and specificity of 71%. Coincidence detection emission tomography can identify malignant mesothelioma in selected subjects exposed to asbestos. Coincidence detection emission tomography appears to be a useful noninvasive method for the follow-up of subjects with exposure risk of asbestosis.
Computed tomography features of liparitosis: a pneumoconiosis due to amorphous silica. S. Mazziotti, M. Gaeta, C. Costa, et al. 2004;23(2):208-13. PubMed · Publisher

Abstract

The purpose of this study was to describe the radiological features of pleural, parenchymal and mediastinal damage due to occupational inhalation of pumice. In total, 31 workers were evaluated for annual follow-up. Spiral computed tomography (CT) was obtained in the three patients with evident parenchymal abnormalities at chest radiograph. High-resolution computed tomography (HRCT) was performed in the remaining 28 subjects with no radiographical evidence of pleuropulmonary damage or evidence of pleural plaques, in order to exclude parenchymal involvement. Pumice samples were analysed by radiograph diffraction and scanning electron microscopy. Spiral CT showed parahilar conglomerate masses containing fine reticular calcifications in three of 31 (9.7%) patients. HRCT showed several bilateral pleural plaques, without any parenchymal lesion in eight of 28 (28.6%) cases. Statistical analysis indicated correlation between CT findings and pulmonary function, as well as exposure to pumice. The analysis of pumice excluded the presence of asbestos. The findings from this study suggest that pleural plaque may be the only sign of disease in patients with a history of pumice inhalation. However, conglomerate parahilar masses are probably due to exposure to massive amounts of heated pumice, and seem to have different pathogenesis and histopathological characteristics to silicosis.
Increased mortality in COPD among construction workers exposed to inorganic dust. I.A. Bergdahl, K. Torén, K. Eriksson, et al. 2004;23(3):402-6. PubMed · Publisher

Abstract

The aim of this study was to find out if occupational exposure to dust, fumes or gases, especially among never-smokers, increased the mortality from chronic obstructive pulmonary disease (COPD). A cohort of 317,629 Swedish male construction workers was followed from 1971 to 1999. Exposure to inorganic dust (asbestos, man-made mineral fibres, dust from cement, concrete and quartz), gases and irritants (epoxy resins, isocyanates and organic solvents), fumes (asphalt fumes, diesel exhaust and metal fumes), and wood dust was based on a job-exposure matrix. An internal control group with "unexposed" construction workers was used, and the analyses were adjusted for age and smoking. When all subjects were analysed, there was an increased mortality from COPD among those with any airborne exposure (relative risk 1.12 (95% confidence interval (CI) 1.03-1.22)). In a Poisson regression model, including smoking, age and the major exposure groups, exposure to inorganic dust was associated with an increased risk (hazard ratio (HR) 1.10 (95% CI 1.06-1.14)), especially among never-smokers (HR 2.30 (95% CI 1.07-4.96)). The fraction of COPD among the exposed attributable to any airborne exposure was estimated as 10.7% overall and 52.6% among never-smokers. In conclusion, occupational exposure among construction workers increases mortality due to chronic obstructive pulmonary disease, even among never-smokers.
Effects of tobacco smoking on findings in chest computed tomography among asbestos-exposed workers. T. Vehmas, L. Kivisaari, M.S. Huuskonen, et al. 2003;21(5):866-71. PubMed · Publisher

Abstract

This study examined the effects of smoking on the findings in chest computed tomography (CT) in 587 asbestos-exposed construction workers (11 females, 576 males, mean age 62 yrs; 18 never-smokers, 406 exsmokers and 163 current smokers). The workers were imaged with spiral CT and high-resolution CT. A total of 13 radiological signs were scored by three radiologists independently. The workers' medical data, smoking habits and occupational exposures were collected at an interview. The effects of smoking status and smoked pack-yrs (0-87.5) on the CT signs were studied using multivariate analysis adjusted for confounding factors. Smoking increased all emphysema signs and contributed to bronchial wall thickening. Smoking was negatively associated with curvilinear and septal lines as well as with parenchymal bands. In persons who had smoked <10 pack-yrs, smoking was positively related to paraseptal emphysema and to bronchial wall thickening and negatively related to septal lines, subpleural nodules and honeycombing. Smoking was related to several abnormal computed tomography signs even among those with relatively small exposure. Computed tomography can detect changes due to smoking at an early stage.
Occupational and nonoccupational factors associated with high grade bronchial pre-invasive lesions. C. Paris, J. Benichou, S. Bota, et al. 2003;21(2):332-41. PubMed · Publisher

Abstract

Besides tobacco exposure, factors associated with the development of pre-invasive bronchial lesions are not known. Autofluorescence bronchoscopy was used to assess the prevalence of severe dysplasia and carcinoma in situ (SD/CIS) of the proximal bronchial tree in relation to occupational or nonoccupational carcinogen exposure. Among the 241 individuals in this study, the overall prevalence of at least one SD/CIS was 9% (21 subjects). Multivariable analysis revealed significant and independent associations between presence of SD/CIS and: 1) active smoking, relative to former smokers; 2) presence of synchronous invasive lung cancer; 3) duration of asbestos exposure and; 4) exposure to other occupational carcinogens. The independent associations of synchronous lung cancer with severe dysplasia and carcinoma, after adjusting for both occupational and nonoccupational carcinogen exposures, suggest other mechanisms than a field cancerisation may be involved in the carcinogenesis of these pre-invasive lesions. Moreover, active smokers, patients with recently resected invasive lung cancer and workers occupationally exposed to bronchial carcinogens may represent a population of choice for early cancer endoscopic detection programmes in view of their high severe dysplasia and carcinoma prevalence.
Trends in asbestos body counts in bronchoalveolar lavage fluid over two decades. P. Dumortier, J. Thimpont, V. de Maertelaer, et al. 2003;22(3):519-24. PubMed · Publisher

Abstract

As in most western countries, the use of asbestos has decreased in Belgium since the mid 1970's. Successive regulations have lowered the permissible levels of exposure and prohibited the use of various asbestos products. In order to assess the impact of these prevention measures on the pulmonary fibre burden of asbestos-exposed patients, the bronchoalveolar lavage fluid (BALF) asbestos body (AB) analysis database of the authors' laboratory was reviewed for the period 1983-2000. A total of 4,772 cases were considered, of which 95% were males. AB concentration exceeded 1 AB x mL BALF(-1) in 36.1%. There was essentially no change in the mean concentration of AB over the period evaluated. However, the concentrations in individuals with very high levels decreased over time. This was associated with a shift in exposure categories from primary asbestos workers to those exposed during handling of asbestos-containing materials or to asbestos in place in buildings or industrial sites. This is consistent with epidemiological data indicating that the number of severe cases of asbestosis caused by very high cumulated doses decreases but that benign pleural diseases and mesothelioma remain the most frequent asbestos-related diseases. Past prevention measures are not expected to have a measurable influence on the incidence of mesothelioma in the near future.
Asbestos bodies in the sputum of asbestos workers: correlation with occupational exposure. C. Paris, F. Galateau-Salle, C. Creveuil, et al. 2002;20(5):1167-73. PubMed · Publisher

Abstract

A cross-sectional medical survey including collection of three consecutive sputum samples was carried out among 270 retired workers of a textile and friction materials factory, in order to investigate the relationship between asbestos body identification and asbestos exposure. The individual cumulative asbestos exposure, determined by means of a plant-specific job-exposure matrix based on asbestos air measurements in the workshops, proved to be heavy with a mean cumulative exposure of 217 fibres x mL(-1) x yr. Macrophages and asbestos bodies were identified in sputum samples by light microscopy. The lung origin of the sputum, suggested by the presence of macrophages and/or asbestos bodies, was confirmed in 82.6% of subjects, and 53% of these samples were positive for asbestos bodies. The prevalence of asbestos bodies was not related to sex, smoking status or latency. Conversely, multivariate analysis showed a positive relationship with cumulative exposure, duration and intensity of exposure to asbestos, as well as age and time since retirement. These findings suggest that sputum analysis for asbestos bodies may remain a relevant and noninvasive marker of heavy occupational exposure to asbestos, even years after retirement. Owing to the new perspectives in lung cancer screening, it might contribute to the identification of high-risk subjects.
Can semi-automated image cytometry on induced sputum become a screening tool for lung cancer? Evaluation of quantitative semi-automated sputum cytometry on radon- and uranium-exposed workers. W. Marek, N. Kotschy-Lang, A. Muti, et al. 2001;18(6):942-50. PubMed · Publisher

Abstract

The correlations between semi-automated sputum cytometry (ASC), conventional cytology and the final diagnosis was investigated in industrially-exposed workers. Slides of sputum samples from 201 former uranium miners with silicosis, 100 patients with asbestosis, 103 workers resected for lung cancer, and 200 controls (50% smokers), were stained using the Papanicolaou (Pap) method and the Feulgen reaction with thionin. Cytometry was performed using the Cyto-Savant automated system. Atypical nuclei were found in 72 of 404 patient samples, 327 samples were normal and five were inadequate for ASC analysis. Thirteen tumours (Pap IV, Pap V) and 11 cases of severe dysplasia were identified by cytology. Lung cancer was confirmed in 20 patients. Compared to the final diagnosis of lung cancer, the sensitivity of ASC was 75% (15 out of 20) and specificity 89.8% (520 out of 579). The results represent a diagnostic efficiency of 89.3%. The combination of ASC with cytology increased sensitivity to 80% (16 out of 20) without significant loss of specificity (89.7% or 523 out of 581). In this investigation of a limited number of patients with occupational radon or asbestos exposure, semi-automated sputum cytometry appears to be sensitive and reliable for the detection of malignant changes in the tracheobronchial mucosa. Together with conventional cytology, it would be reasonable to test the validity of the combined methods in a large-scale feasibility study of early lung cancer detection.
Observer variation in computed tomography of pleural lesions in subjects exposed to indoor asbestos. H. De Raeve, J.A. Verschakelen, P.A. Gevenois, et al. 2001;17(5):916-21. PubMed · Publisher

Abstract

To assess the reliability of computed tomography (CT) in detecting discrete pleural lesions, the interobserver and intra-observer variability in reading the conventional and high-resolution CT (HRCT) scans of 100 volunteers, who had worked for > or = 10 yrs in a building with known asbestos contamination, was evaluated. In the first session, pleural abnormalities were detected by a single radiologist (A1) in 13 subjects. In the second session, the scans were read again independently by the same radiologist (A2) and two other experienced radiologists (B, C). The final decision for the presence of pleural lesions was made in a final consensus reading. This gave a diagnosis of pleural abnormalities in 18 subjects, of whom eight (44%) had been detected by all three readers, five (28%) by two readers and four (22%) by only one reader; one scan, rated normal by all readers during the second session, was reconsidered because pleural abnormalities had been noted at the first reading (A1). The intra-observer agreement for reader A was good (kappa (kappa) 0.68) but the interobserver agreement between the readers was only fair to moderate (weighted kappa: A2-B=0.43, A2-C = 0.45, B-C = 0.26) in the second reading session. In conclusion, when looking for the prevalence of pleural lesions in indoor asbestos exposed subjects, the potential lack of consistency in reporting the presence of small pleural abnormalities must be borne in mind and strict precautions must be taken.
The role of environmental and occupational exposures in Turkish immigrants with fibre-related disease. P. Dumortier, A. Göcmen, K. Laurent, et al. 2001;17(5):922-7. PubMed · Publisher

Abstract

Environmental exposure to tremolite and erionite causes endemic diseases of the lung and pleura in Turkey. This study aimed to evaluate the impact of these exposures and further occupational exposures on fibre-related diseases in Turkish immigrants living in Belgium. The study included 51 males and 17 females that emigrated < 1-38 yrs ago. Most of them (n=46) had nonmalignant pleural lesions, one had asbestosis and one had mesothelioma. Environmental asbestos exposure was likely for the majority of patients (60%), but there were also reports of possible occupational asbestos (n = 14) and erionite (n = 2) exposure. Tremolite was the main fibre type in bronchoalveolar lavage fluid (BALF). Elevated concentrations of amosite or crocidolite were detected in only two patients. The delay elapsed since the end of the environmental exposure had no influence on the asbestos body or the tremolite fibre concentrations in the BALF of Turkish immigrants. Most fibre-related diseases in Turkish immigrants are probably due to environmental rather than occupational exposure. Precise information about geographical origin and occupation should be obtained when investigating these patients. Mineralogical analysis of bronchoalveolar lavage fluid gives valuable information on the type and intensity of exposure, especially in patients with both environmental and occupational exposure.
Lung sounds in asbestos induced pulmonary disorders. P. Piirilä, H. Lehtola, A. Zitting, et al. 2000;16(5):901-8. PubMed · Publisher

Abstract

The aim of the study was to compare the lung sounds in patients with asbestos related pulmonary disorders with findings in high-resolution computed tomography (HRCT), and with lung function variables, in order to find out associations of acoustic changes with radiological fibrosis, emphysema or with pulmonary gas transfer functions. Sixty-four patients with asbestos-related pleural disease, with or without pulmonary disease, were studied. Lung sound recording and analysis was carried out with a computerized lung sound analyser, and HRCT of the chest, as well as forced spirometry and diffusing capacity measurement were performed. The fibrosis score correlated positively with the quartile frequencies of the power spectrum of lung sounds in inspiration (f50) and expiration (f50) and crackle count in inspiration, as well as negatively with diffusing capacity. When the patients with crackling sounds and significant fibrosis were excluded (n=18), emphysema correlated negatively with expiratory quartile frequencies of the power spectrum, with f25 and f50. Furthermore, diffusing capacity correlated with inspiratory f25 and forced expiratory volume in one second with inspiratory f50 when crackles and fibrosis were excluded. Changes in lung sounds were significantly associated with radiologically verified abnormalities and gas transfer of pulmonary tissue. High sound frequencies were associated with fibrotic changes of the lung while low sound frequencies with pulmonary emphysema. Acoustic analysis gives complementary clinical information for evaluation of asbestos-related pulmonary disorders.

1990s

Carboxyterminal propeptide of type I procollagen in ELF: elevation in asbestosis, but not in pleural plaque disease. L. Lammi, L. Ryhänen, E. Lakari, et al. 1999;14(3):560-4. PubMed · Publisher

Abstract

Markers of collagen metabolism may possibly be used in the assessment of pulmonary involvement in asbestosis-related pulmonary diseases. In this study the levels of the carboxyterminal propeptide of type I procollagen (PICP) and the aminoterminal propeptide of type III procollagen (PIIINP) were evaluated in bronchoalveolar lavage fluid (BALF), epithelial lining fluid (ELF) and serum from patients with asbestos related pulmonary and pleural involvement. Forty-two consecutive patients with occupational exposure to asbestos fibres, who underwent bronchoscopy and bronchoalveolar lavage (BAL) at the time of the diagnosis were investigated. Five patients were diagnosed as having asbestosis, while 37 showed no parenchymal involvement. Of the latter group, 25 had pleural plaques, while 12 had no detectable changes in chest radiographs. The patients were followed-up for an average of 7 yrs. The PICP in BALF and ELF was detectable in all patients with asbestosis and in 8/37 subjects without parenchymal involvement. The levels of PICP in BALF and ELF were significantly higher in the asbestosis group compared to the patients without asbestosis (9.8+/-1.8 microg x L(-1) versus 0.6+/-1.3 microg x L(-1), p<0.001 and 488.9+/-208.8 microg x L(-1) versus 22.6+/-50.6 microg x L(-1), p<0.001, respectively). Only 1 patient with asbestosis and 3 patients without parenchymal involvement had detectable levels of PIIINP in BALF. The serum levels of PICP and PIIINP did not differ between the patients with asbestosis and those with exposure to asbestos fibres without asbestosis and were within the normal range. None of the 37 patients exposed to asbestos fibres without parenchymal involvement at the baseline developed asbestosis during the follow-up period of 7 yrs. In conclusion, the data show that the carboxyterminal propeptide of procollagen type I, but not the aminoterminal propeptide of type III procollagen is highly elevated in bronchoalveolar lavage fluid and epithelial lining fluid in patients with asbestosis, but not in those without parenchymal involvement. This suggests that the determination of carboxyterminal propeptide of procollagen type I in bronchoalveolar lavage fluid could be used as a marker of parenchymal involvement in patients exposed to asbestos fibres.
Low dose cabergoline induced interstitial pneumonitis. W. Frank, R. Moritz, B. Becke, et al. 1999;14(4):968-70. Case report PubMed · Publisher

Abstract

Certain dopaminergic anti-Parkinson drugs (ergolines) have repeatedly been identified as a cause of pleuropulmonary disease with a focus on serosal cell damage. Recently, a pathogenetic link between ergolines and prior asbestos exposure was suggested, as regards the development of pleural pathology. This report describes a patient with idiopathic Parkinson's disease, who was on a multiple drug regimen including low dose cabergoline. The patient developed a febrile illness with widespread bilateral lung infiltrations nonresponsive to beta-lactam and macrolide antibiotics. Bronchoalveolar lavage and transbronchial lung biopsy showed a "hypersensitivity-like" interstitial lung disease, which cleared almost completely within 2 months after simple drug withdrawal. Circumstantial evidence suggests a so far undescribed adverse lung reaction to cabergoline, devoid of the more usual pleural changes.
Oxidant and antioxidant mechanisms of lung disease caused by asbestos fibres. V.L. Kinnula. 1999;14(3):706-16. Review PubMed · Publisher

Abstract

The pathogenesis of asbestos-related lung diseases is complicated and still poorly understood. Studies on animal models and cell cultures have indicated that asbestos fibres generate reactive oxygen and nitrogen species and cause oxidation and/or nitrosylation of proteins and deoxyribonucleic acid as a marker of cell injury. These effects are potentiated by the inflammation caused by the fibres. Recent studies have shown that individual variability in the antioxidant and/or detoxifying mechanisms probably has an important role in the development of asbestos-related lung diseases. Asbestos fibres cause both cell proliferation and apoptosis by multiple mechanisms, one of them being activation of signal transduction pathways by reactive oxygen and nitrogen species. Asbestos activates transcription factors such as nuclear factor kappa B, which has been shown to lead to the upregulation of antioxidant enzymes, most importantly manganese superoxide dismutase. This enzyme is also overexpressed in asbestos-related human malignant mesothelioma, whereas the induction of other antioxidant enzymes (copper-zinc superoxide dismutase, catalase, glutathione peroxidase) by asbestos fibres appears to be marginal. The significance of antioxidant enzymes in asbestos related diseases has, however, remained unclear. Furthermore, previous studies have not been able to offer successful therapies to the patients with asbestos-associated diseases. Only an improved understanding of the pathogenetic mechanisms in the human lung provides a basis for future therapies for asbestos-related diseases.
Asbestos, ergot drugs and the pleura. P. Camus, G. Hillerdal, P. De Vuyst. 1998;11(6):1427. Comment · Letter PubMed · Publisher
Asbestosis, pleural plaques and diffuse pleural thickening: three distinct benign responses to asbestos exposure. P.A. Gevenois, V. de Maertelaer, A. Madani, et al. 1998;11(5):1021-7. PubMed · Publisher

Abstract

The aim of this study was to investigate by computed tomography (CT) whether asbestosis, diffuse pleural thickening and/or pleural plaques are statistically associated. We also tried to find criteria to differentiate between diffuse and circumscribed pleural thickening. From 231 exposed workers, only those subjects whose radiograph showed neither bilateral calcified pleural plaques nor small pulmonary opacities higher than 1/1 grade according to the 1980 International Labour Office (ILO) Classification were considered. Scans were assessed for the presence of subpleural curvilinear lines, septal and intralobular lines, parenchymal bands, honeycombing, rounded atelectasis, pleural plaques and diffuse pleural thickening. CT scans revealed pleural and/or lung abnormalities in 99 workers. Pleural plaques were unilateral in one-third of cases with plaques. Diffuse pleural thickening, parenchymal bands and rounded atelectasis were unilateral in, respectively, 62 and 69 and 75% of cases with the abnormality. Septal and intralobular lines, and honeycombing were always bilateral. CT signs could be grouped into three patterns: 1) septal and intralobular lines, and honeycombing corresponding to pulmonary fibrosis; 2) pleural plaques corresponding to parietal pleural fibrosis; and 3) diffuse pleural thickening, rounded atelectasis and parenchymal bands corresponding to visceral pleural fibrosis. In these workers with a normal or near-normal radiograph, three groups of subjects with different responses were distinguished. Crow's feet and rounded atelectasis help to differentiate plaques from diffuse thickening.
Effectiveness of postal smoking cessation advice: a randomized controlled trial in young men with reduced FEV1 and asbestos exposure. S. Humerfelt, G.E. Eide, G. Kvåle, et al. 1998;11(2):284-90. Randomized trial PubMed · Publisher

Abstract

There have been few community-based randomized, controlled intervention trials for cessation in high-risk smokers. In such a trial we evaluated the effects of postal smoking cessation advice in smokers with asbestos exposure and/or reduced forced expiratory volume in one second (FEV1). All men aged 30-45 yrs (n=22,392) living in 34 municipalities in western Norway were invited to a cross-sectional community survey. Information on smoking habits and occupational asbestos exposure were obtained from self-administered questionnaires and measurements of FEV1 were performed with dry-wedge bellow spirometers. Among 16,393 participants we identified a group of 2,610 smokers with previous occupational asbestos exposure and/or adjusted FEV1 in the lowest quartile. A random half (n=1,300) received a mailed personal letter from a respiratory physician with a person-specific health advice to quit smoking and a pamphlet on smoking cessation. The remaining smokers (n=1,310) acted as controls and did not receive any information. Twelve months after the intervention, information on smoking habits was re-examined using a postal questionnaire. Among the respondents (n=2,282), smoking cessation was reported altogether by 13.7% in the intervention group versus 9.9% in the control group (p<0.01). The 1 yr sustained quit rate (no smoking at all during the last year) was 5.6 versus 35% (p<0.05), respectively. Measurements of carbon monoxide in expired air (with < or = 10 parts per million) confirmed self-reported nonsmoking in samples of the two groups. In a community this simple postal smoking cessation advice from a respiratory physician based on person-specific risk factors improved the 1 yr sustained success rate by 60% in identified high-risk smokers.
Guidelines for mineral fibre analyses in biological samples: report of the ERS Working Group. European Respiratory Society. P. De Vuyst, A. Karjalainen, P. Dumortier, et al. 1998;11(6):1416-26. PubMed · Publisher

Abstract

Microscopic techniques for analysing asbestos fibres in lung tissue and bronchoalveolar lavage have provided major information in the understanding of asbestos-related diseases. These analyses are increasingly applied for clinical work and medicolegal problems. Differences in sampling, preparation and counting techniques, definitions of reference populations and expression of results have caused major difficulties in comparing results from different laboratories. Therefore it appeared necessary to set a goal to harmonize these analyses between the European laboratories active in this field. This article summarizes the work of a European Respiratory Society working group with participation from nine European laboratories. The five main issues touched upon are: 1) definitions of control populations and reference levels; 2) sampling, preparation and analytical techniques; 3) asbestos fibres in lung tissues in different pathologies; 4) asbestos bodies in lung tissue, bronchoalveolar lavage and sputum; and 5) basis for the interpretation of fibres and asbestos bodies in biological samples. These guidelines indicate the crucial importance of several factors for the interpretation of the results; namely, adequate sampling, comparable analytical procedures and expression of the results, the use of well-defined reference populations, and a comprehensive understanding of the factors affecting the fibre retention and the dose-responses associated with the different asbestos-related diseases.
Magnetic resonance imaging of the thorax in the evaluation of asbestosis. S.I. Bekkelund, U. Aasebø, C. Pierre-Jerome, et al. 1998;11(1):194-7. PubMed · Publisher

Abstract

The purpose of the study was to evaluate the accuracy of magnetic resonance imaging (MRI) in detecting subclinical morphological changes caused by asbestos exposure. Conventional chest radiographs according to the International Labour Organisation (ILO) categories 0-11 and spirometric data were compared with MRI in 17 men with mean (+/-2SD) asbestos exposure time of 24.6+/-13.0 yrs. Mean age was 62.0+/-9.4 yrs. The inclusion criterion was an ILO score of 2 or more. Electrocardiographic registrations and antirespiratory movement artefact techniques were used in all MRI examinations to avoid movement artefacts. Mean ILO grading was found to be 7.7+/-3.8 on chest radiography and 9.8+/-2.0 with MRI (p=0.01). Five patients had a higher ILO stage as evaluated by MRI, but in nine patients the staging remained unchanged. MRI revealed mediastinal adenopathy in four patients. Forced expiratory volume in one second (expressed as a percentage of the predicted value) was negatively correlated with ILO score as assessed by MRI (r=-0.4, p=0.032). Magnetic resonance imaging seems to be more sensitive than conventional radiographs in detecting subclinical fibrosis as well as the extent of pleural asbestosis.
Malignant pleural mesothelioma. C. Boutin, M. Schlesser, C. Frenay, et al. 1998;12(4):972-81. Review PubMed · Publisher

Abstract

The incidence of malignant pleural mesothelioma (MPM) has risen for some decades and is expected to peak between 2010 and 2020. Up to now, no single treatment has been proven to be effective and death usually occurs within about 12-17 months after diagnosis. Perhaps because of this poor prognosis, early screening has incited little interest. However, certain forms may have a better prognosis when diagnosed early and treated by multimodal therapy or intrapleural immunotherapy. Diagnosis depends foremost on histological analysis of samples obtained by thoracoscopy. This procedure allows the best staging of the pleural cavity with an attempt to detect visceral pleural involvement, which is one of the most important prognostic factors. Although radiotherapy seems necessary and is efficient in preventing the malignant seeding after diagnostic procedures in patients, there has been no randomized phase III study showing the superiority of any treatment compared with another. However, for the early-stage disease (stage I) a logical therapeutic approach seems to be neoadjuvant intrapleural treatment using cytokines. For more advanced disease (stages II and III) resectability should be discussed with the thoracic surgeons and a multimodal treatment combining surgery, radiotherapy and chemotherapy should be proposed for a randomized controlled study. Palliative treatment is indicated for stage IV. In any case, each patient should be enrolled in a clinical trial.
The priority for recognizing asbestos as a multicentre carcinogen, and problems in categorizing asbestos tumours. M. Greenberg. 1998;11(4):996. Comment · Letter PubMed · Publisher
Asbestos, ergot drugs and the pleura. P. De Vuyst, P. Pfitzenmeyer, P. Camus. 1997;10(12):2695-8. Comment · Editorial · Review PubMed · Publisher

Summary

This editorial accompanied two reports in the same journal issue. Those reports described patients with past occupational asbestos exposure who developed exudative pleural effusion and/or pleural thickening while taking bromocriptine for Parkinson's disease. The pleural changes were largely reversible after the drug was stopped. The authors noted that neither report included a control group, so any interaction between asbestos and ergot drugs (ergolines) remained speculative. They reviewed the pleural lesions linked to asbestos and the pleuropulmonary changes caused by long-term ergoline treatment. Compared with asbestos-related changes, ergoline-induced changes rarely, if ever, calcified, developed more quickly, and were often accompanied by a markedly raised erythrocyte sedimentation rate (mean 55.0 versus 25.7 mm in two earlier series). The main difference was improvement after the drug was withdrawn. The authors described four situations in former asbestos workers taking ergolines. In the first three, pleural plaques, chronic thickening with calcifications and slowly developing thickening without calcifications, they favoured asbestos as the cause. In the fourth, pleural effusion, they called the work-up most difficult and proposed a stepwise approach that included pleural biopsy or thoracoscopy to rule out mesothelioma. They reported that steroids had shown no clear benefit. They concluded that epidemiological evidence was still awaited, and that progressive pleural disease in asbestos-exposed patients should prompt a search for reversible causes such as ergoline treatment.

PubMed has no abstract for this study, and the article doesn't print one. We wrote this summary from the full article with the help of AI. It is not the authors' wording.
History of mesothelioma. M. Greenberg. 1997;10(11):2690-1. Comment · Historical article · Letter PubMed · Publisher
Pleural disease during treatment with bromocriptine in patients previously exposed to asbestos. G. Hillerdal, J. Lee, A. Blomkvist, et al. 1997;10(12):2711-5. Case report PubMed · Publisher

Abstract

Bromocriptine, which is used in the treatment of Parkinson's disease, can cause adverse pleuropulmonary reactions. Exposure to asbestos can result in similar lesions. Fifteen patients with former exposure to asbestos, who developed pleural fibrosis after treatment with bromocriptine, were observed independently in Sweden (11 patients) and Australia (four patients). The patients complained of malaise, often associated with weight loss, dyspnoea, and a disturbing cough. Laboratory values included increased erythrocyte sedimentation rate and a low haemoglobin level. Lung function tests showed a restrictive lung function defect. Chest radiographs showed bilateral pleural fibrosis, with small amounts of fluid in some cases. Soon after bromocriptine was withdrawn, the patients improved clinically, and the laboratory values returned to normal. However, in most cases, pleural fibrosis and a restrictive lung function defect persisted to some extent. In conclusion, in patients who develop pleuropulmonary fibrosis whilst being treated with bromocriptine, former exposure to asbestos should be investigated. Conversely, when pleural changes develop in a patient on bromocriptine and with prior exposure to asbestos, the possible causative role of the drug should be discussed. Special follow-up may be indicated when bromocriptine is planned in a patient with previous asbestos exposure, and if symptoms or signs of pleural fibrosis develop, bromocriptine withdrawal should be considered.
Pleural effusion during bromocriptine exposure in two patients with pre-existing asbestos pleural plaques: a relationship?. C. Knoop, M. Mairesse, C. Lenclud, et al. 1997;10(12):2898-901. Case report PubMed · Publisher

Abstract

Two patients with pleural plaques developed pleural effusion and subsequent diffuse pleural fibrosis 50 and 39 yrs after their first exposure to asbestos. The diagnosis of benign asbestos pleural effusion was suggested, but the work-up finally suggested bromocriptine-induced pleural disease in both patients. These two cases illustrate that drug-induced pleural effusion is an important differential diagnosis of benign asbestos pleural effusion. It is, moreover, possible that pre-existing asbestos pleural lesions, or even asbestos exposure, increases the risk of developing bromocriptine-induced pleural disease.
Asbestos bodies in bronchoalveolar lavage in relation to asbestos bodies and asbestos fibres in lung parenchyma. A. Karjalainen, R. Piipari, T. Mäntylä, et al. 1996;9(5):1000-5. PubMed · Publisher

Abstract

In Finland, unlike other countries, anthophyllite asbestos has been widely used due to its domestic production in 1918-1975. In this particular context, the aim of the present study was to analyse the relationship between asbestos bodies (ABs) in bronchoalveolar lavage (BAL) fluid and the concentration of ABs and the different amphibole asbestos fibres in lung tissue. Sixty five BAL lung tissue sample pairs from patients with pulmonary disease were analysed. The concentration of ABs in BAL fluid and lung tissue was determined with optical microscopy, and the concentration, type and dimensions of asbestos fibres in lung tissue with scanning electron microscopy. There was a significant correlation between the concentrations of ABs in BAL fluid and in lung tissue (r = 0.72; p < 0.001), between the concentrations of ABs and amphibole asbestos fibres in lung tissue (r = 0.73; p < 0.001), and between the concentration of ABs in BAL fluid and the concentration of amphibole asbestos fibres in lung tissue (r = 0.64; p < 0.001). In patients who had been exposed mainly to commercial anthophyllite, significantly higher concentrations of ABs were observed per total pulmonary amphibole fibre burden, as compared to patients whose main exposure was to crocidolite/amosite. The anthophyllite fibres in lung tissue were longer than the crocidolite/amosite fibres. The relationship between asbestos body counts in lung tissue and in bronchoalveolar lavage fluid was similar to previous international observations. When using the asbestos body count to predict the underlying total pulmonary amphibole asbestos burden in Finnish patients, however, it should be borne in mind that the relationship between the two parameters seems to be different with anthophyllite as compared to crocidolite/amosite fibres.
Malignant pleural mesothelioma from nonoccupational asbestos exposure in Metsovo (north-west Greece): slow end of an epidemic?. K. Sakellariou, V. Malamou-Mitsi, A. Haritou, et al. 1996;9(6):1206-10. PubMed · Publisher

Abstract

Inhabitants of the Metsovo area, north-west Greece have been exposed since childhood to inhalation of asbestos, from a material containing tremolite, used for whitewashing ("luto soil"). This has resulted in endemic pleural calcifications (47% of adult population) and increased incidence of malignant pleural mesothelioma (MPM). In 1987, we reported that the incidence of MPM between 1981-1985 was around 300 times higher than expected in a nonasbestos exposed population (seven cases in 5 yrs in a population of 4,000-5,000). The present study is an updated report regarding this "mesothelioma epidemic", in conjunction with the diminished use and final abandonment of "luto soil" in the early 1980s. It appears that the incidence of MPM in Metsovo has dropped considerably since our first report. Between 1985-1994, we diagnosed six such cases (incidence rate = 1.4 cases per 10,000 person-years), whilst between 1980-1984 eight cases had been diagnosed (incidence rate = 3.7 cases per 10,000 person-years). Although, because of the small number of cases, this did not reach statistical significance (p = 0.08), we note that the incidence is now considerably lower than before. Had it remained unchanged, we would have expected 17 cases of MPM instead of six. This drop follows the diminished use of "luto" whitewash (by 92% of the population in 1950 and only 18% in 1980). If we take into account a 30-40 year latency period for mesothelioma, we expect that the "Metsovo mesothelioma epidemic" will fade away by the year 2020-2030, since the material has not been used since 1985.
Relevance of asbestos bodies in sputum. H. Teschler, A.B. Thompson, R. Dollenkamp, et al. 1996;9(4):680-6. PubMed · Publisher

Abstract

The presence of asbestos bodies (ABs) in sputum specimens of individuals with occupational asbestos exposure has been well-documented. The aim of this study was to determine their clinical relevance in comparison to the concentration of AB in bronchoalveolar lavage (BAL) and lung tissue. Subjects were included following a well-documented exposure of asbestos history (n = 93) or BAL fluid analysis positive for ABs (n = 42). The subjects with a well documented history of AB exposure were divided into three groups: heavy (Group 1, n = 29); moderate (Group 2, n = 31); or occasional exposure (Group 3, n = 33). BAL fluid was available from all subjects, and lung tissue from 21 subjects. To assess the variability, 10 sputum positive subjects collected subsequent sputum on days 2, 7, 14, 30 and 90. ABs were determined by light microscopy after membrane filtration of specimen digests. The mean sputum AB content was highest in Group 1 (2.4 +/- 5.5 AB.mL-1), lower in Group 2 (0.2 +/- 0.3 AB.mL-1) and lowest in Group 3 (0.1 +/- 0.1 AB.mL-1) suggesting a correlation with cumulative exposure. However, many negative sputum samples were noted, when BAL specimens were positive. The AB content of sputum and BAL specimens did not correlate. ABs were found in sputum of all subjects with a tissue content of > 1,000 AB-cm-3, but in none with contents of < 1,000 AB-cm-3. Substantial variability of ABs was found in the five sequentially collected sputa of 10 initially positive patients (coefficient of variation 28-93%), but only two false negatives were found in these 50 samples. Thus, sputum analysis for asbestos bodies is an insensitive method for assessing the lung asbestos burden, much less sensitive than bronchoalveolar lavage fluid analysis. However, a sputum sample positive for asbestos bodies is suggestive of a high lung asbestos burden.
The epidemiology of mesothelioma in historical context. J.C. McDonald, A.D. McDonald. 1996;9(9):1932-42. Historical article · Review PubMed · Publisher

Abstract

Primary malignant mesothelial tumours were recognized by pathologists before asbestiform minerals (chrysotile, crocidolite and amosite) were mined commercially. The discovery, 40 yrs ago, of a causal link with crocidolite and the wide-ranging epidemiological studies which followed are the subject of this review. Early case-control and descriptive surveys, supplemented by cohort studies in insulation workers and chrysotile miners, quickly demonstrated major occupational and geographical differences, with high risk in naval dockyard areas and in the heating trades. In the 1980s, reliable cohort surveys showed that in mining and in the manufacture of asbestos products the mesothelioma risk was much higher when exposure included crocidolite or amosite than chrysotile alone. However, qualitative and quantitative information on exposure was too often inadequate for this evidence to be conclusive. Well-controlled lung fibre analyses have reduced these deficiencies and demonstrated the probable implications of the greater biopersistence of amphibole fibres. Chrysotile for industrial use often contains low concentrations of fibrous tremolite, which may well explain the few cases of mesothelioma associated with this type of asbestos. Progress in this field has been much retarded by controversy, for which the 20 year gap between the availability of reliable estimates of risk for the mining of chrysotile and that for crocidolite or amosite may have been largely responsible.
Biological and immunological aspects of malignant mesothelioma. M.J. Garlepp, C.C. Leong. 1995;8(4):643-50. Review PubMed

Abstract

Malignant mesothelioma (MM) is an aggressive tumour, which is strongly associated with previous asbestos exposure and is resistant to all conventional anticancer therapies. An understanding of the biological properties of MM may provide insights into useful therapeutic strategies, and MM cell lines and animal models have been major contributors to our current knowledge of this tumour. Although karyotypic abnormalities are frequent, there is no clear evidence of a mesothelioma-specific chromosomal aberration. Similarly, there is no evidence of activation or over-expression of a known oncogene, or of the inactivation of currently identified tumour suppressor genes. A number of growth factors, including platelet derived growth factors A and B (PDGF-A and -B), insulin-like growth factor I and transforming growth factor-beta (TGF-beta), and some of their receptors, have been reported to be expressed by MM cells, and each has the potential to play a role as a growth stimulant for MM or to modify immune responses to the tumour. Some data support an autocrine role for PDGF-A. MM cell lines are susceptible to lysis by a variety of immune effector cells, and their growth can often be inhibited by cytokines. The possibility of stimulating an immune response to MM by genetic manipulation of the tumour cells has been investigated using a murine model. The data so far suggest that transfection of allogeneic class I major histocompatibility complex genes or syngeneic class II genes alone is unlikely to induce protective immunity.(ABSTRACT TRUNCATED AT 250 WORDS)
Lung surfactant protein-A and carcinoembryonic antigen in pleural effusions due to lung adenocarcinoma and malignant mesothelioma. N. Shijubo, Y. Honda, T. Fujishima, et al. 1995;8(3):403-6. PubMed · Publisher

Abstract

Lung surfactant protein-A (SP-A) is a major phospholipid-associated glycoprotein in surfactant, and is a useful immunohistochemical marker for lung adenocarcinoma. Carcinoembryonic antigen (CEA) has not been immunohistochemically detected in mesothelioma. In pleural effusions due to malignant mesothelioma, very low concentrations of SP-A and CEA can be expected. We studied the value of combined determinations of CEA and SP-A in pleural fluid to distinguish between lung adenocarcinoma and mesothelioma. SP-A and CEA concentrations were measured in pleural effusions from 78 patients with lung adenocarcinoma and 10 with malignant mesothelioma. SP-A concentrations in pleural effusions due to lung adenocarcinoma and mesothelioma were 516 +/- 140 and 16.9 +/- 3.6 ng.ml-1 (mean +/- SEM), respectively. CEA concentrations in pleural effusions due to lung adenocarcinoma and mesothelioma were 239 +/- 92.4 and 1.7 +/- 0.3 ng.ml-1, respectively. SP-A values did not exceed 100 ng.ml-1 in any of 10 mesotheliomas, whilst in 37 of 78 lung adenocarcinomas they did. CEA values did not exceed 10 ng.ml-1 in any of 10 mesotheliomas, whilst in 53 of 78 lung adenocarcinomas they did. Increased values of SP-A and/or CEA were found in pleural effusions from 67 of 78 lung adenocarcinomas. It is concluded that a combination of CEA and SP-A assays in pleural effusions will be helpful for discriminating lung adenocarcinoma from mesothelioma.
Respiratory health effects of man-made vitreous (mineral) fibres. P. De Vuyst, P. Dumortier, G.M. Swaen, et al. 1995;8(12):2149-73. Review PubMed · Publisher

Abstract

The group of man-made mineral or vitreous fibres (MMMFs or MMVFs) includes glass wool, rock wool, slag wool, glass filaments and microfibres, and refractory ceramic fibres (RCFs). Experimental observations have provided evidence that some types of MMVF are bioactive under certain conditions. The critical role of size parameters has been demonstrated in cellular and animal experiments, when intact fibres are in direct contact with the target cells. It is, however, difficult to extrapolate the results from these studies to humans since they bypass inhalation, deposition, clearance and translocation mechanisms. Inhalation studies are more realistic, but show differences between animal species regarding their sensibility to tumour induction by fibres. Fibre biopersistence is an important factor, as suggested by recent inhalation studies, which demonstrate positive results with RCF for fibrosis, lung tumours and mesothelioma. There is no firm evidence that exposure to glass-, rock- and slag wool is associated with lung fibrosis, pleural lesions, or nonspecific respiratory disease in humans. Exposure to RCF could enhance the effects of smoking in causing airways obstruction. An elevated standard mortality ratio for lung cancer has been demonstrated in cohorts of workers exposed to MMVF, especially in the early technological phase of mineral (rock slag) wool production. During that period, several carcinogenic agents (arsenic, asbestos, polycyclic aromatic hydrocarbons (PAH)) were also present at the workplace and quantitative data about smoking and fibre levels are lacking. It is not possible from these data to determine whether the risk of lung cancer is due to the MMVFs themselves. No increased risk of mesothelioma has been demonstrated in the cohorts of workers exposed to glass-, slag- or rock wool. There are in fact insufficient epidemiological data available concerning neoplastic diseases in RCF production workers because of the small size of the workforce and the relatively recent industrial production.
Implantable access system for prolonged intrapleural immunotherapy. P. Driesen, C. Boutin, J.R. Viallat, et al. 1994;7(10):1889-92. PubMed · Publisher

Abstract

We describe our experience using an implantable Port-A-Cath access system for intrapleural administration of gamma-interferon (gamma-IFN) in malignant mesothelioma patients. Twenty nine patients, with histologically proven malignant mesotheliomas were included in this study. To avoid complications the device was implanted in a subcutaneous pocket, and the catheter was connected via a tunnel. Also, a suction drain was installed in the pocket after placement. This procedure greatly reduced the high infection rate (64%) encountered with conventional open chest tubes. Patients' tolerance was excellent and maintenance minimal. In our opinion, the Port-A-Cath system is the most suitable device for intra-cavitary long-term therapy of malignant pleural effusions.
Longitudinal changes in time domain spirogram indices and their variability. T. Nakadate, T. Sato, J. Kagawa. 1994;7(6):1062-9. PubMed

Abstract

The purpose of this study was to describe longitudinal changes in time domain spirogram indices and their variability. We therefore measured forced expiratory spirograms of 326 middle-aged male employees in two asbestos-using factories four times over 5 yrs. From the original sample of 326, 225 healthy subjects, who provided reliable results for three or more surveys, were selected for analysis. The mean and standard deviation of transit time and their log-transformed values (MTT, STT, ln(MTT), and ln(STT), respectively), as well as two indices of the estimated time constant distribution (Mu and Sigma, respectively) were analysed using a longitudinal model. The longitudinally estimated annual increase of MTT, STT, ln(MTT), and ln(STT) was about three times larger than the cross-sectional estimate, whilst they were comparable in Mu and Sigma. A highly significant contribution of between-subject variability was found in all indices. This was particularly remarkable in the mean components. The between-subject variability was about eight times larger than the error variance in Mu, and three times in MTT and ln(MTT). We conclude that the longitudinal data of transit time indices should not be compared with cross-sectional reference values, and that the magnitude of error variance of these indices in longitudinal repeated measurements will be rather less than the cross-sectional counterpart reported previously.

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