Thorax

About the journal

Publisher: British Medical Assn
Published: 1946 to the present, England
Language: English
ISSN: 0040-6376 (print), 1468-3296 (electronic)
Its record in the NLM Catalog

2020s

Coexposure to asbestos, mineral wool, crystalline silica and refractory ceramic fibres and risk of lung cancer and mesothelioma. F. Delva, C. Gramond, I. Thaon, et al. 2026;81(5):430-438. PubMed · Publisher · Free full text

Abstract

Background: Asbestos, mineral wool (MW), refractory ceramic fibres (RCF) and silica are among the most common exposures to mineral particles in the workplace.

Objective: To study the effect of coexposure to asbestos and MW, crystalline silica or RCFs and the risk of lung cancer and mesothelioma.

Methods: The Asbestos-Related Diseases Cohort is a surveillance programme in retired workers exposed to asbestos during their working life. Complete job histories were collected and occupational exposure to asbestos was assessed by an expert, while occupational exposure to MW, RCFs and silica was assessed using French job-exposure matrices. Cox proportional hazards models were used to estimate HR and 95% CI for lung cancer mortality and lung cancer incidence and for mesothelioma mortality or mesothelioma incidence.

Results: In this population of workers exposed to asbestos, in the mortality study, exposures to MW, crystalline silica and RCFs were not found to be associated with lung cancer after adjustment for smoking and asbestos, nor with mesothelioma after adjustment for asbestos. In the incidence study, there was an association between exposure to crystalline silica (ever exposed) and mesothelioma (HRa=1.75, 95% CI 1.17 to 2.62).

Conclusion: Crystalline silica is not known to induce mesothelioma but coexposure to asbestos could increase the effect of asbestos on the mesothelial cells.

© Author(s) (or their employer(s)) 2026. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group.
Inhalational exposures associated with risk of interstitial lung disease: a systematic review and meta-analysis. C.T. Lee, S.A. Gandhi, S. Elmrayed, et al. 2025;80(12):918-926. Systematic review · Meta-analysis PubMed · Publisher · Free full text

Abstract

Rationale: Inhalational exposures are associated with risk of developing interstitial lung disease (ILD), yet the relationship between specific exposures and ILD is poorly characterised.

Objective: Identify inhalational exposures associated with ILD and estimate the effects of exposures on ILD risk.

Methods: MEDLINE and EMBASE databases were searched from 1990 to 2022 to identify inhalational exposures associated with ILD diagnosis. ILDs where causality is well-established (hypersensitivity pneumonitis, pneumoconiosis) and sarcoidosis were excluded. Two independent reviewers screened abstracts with full-text review and data extraction of eligible studies. Where possible, data were pooled and multilevel meta-analysis was specified using a random effects model. Sources of heterogeneity and risk of bias were assessed.

Main Results: 96 studies were included in the systematic review, representing 40 819 116 subjects (295 167 had ILD, 40 523 949 controls). For the meta-analysis, 54 studies were included (40 490 793 subjects: 273 899 ILD, 40 216 894 controls). Exposures associated with significantly increased ILD risk included smoking (OR 1.69, 95% CI 1.47 to 1.94), organic exposures (OR 1.56, 95% CI 1.12 to 2.16), metals (OR 1.52, 95% CI 1.07 to 2.16), dust (OR 1.45, 95% CI 1.20 to 1.76) and asbestos (OR 1.53, 95% CI 1.08 to 2.15). Silica and fumes had positive associations with ILD that trended towards significance.

Conclusions: This systematic review and multilevel meta-analysis is the first to comprehensively assess the effect of inhalational exposures on overall risk of ILD, with multiple putative exposures identified. Future work should investigate novel occupational exposures associated with ILD, characterise the gene-environment interaction and develop preventative strategies.

Prospero Registration Number: CRD42022292908.

© Author(s) (or their employer(s)) 2025. No commercial re-use. See rights and permissions. Published by BMJ Group.
Well-differentiated papillary mesothelial tumour: a rare finding on the pleura. L. Rostock, O. Holotiuk, T. Ploenes. 2024;79(4):380-381. PubMed · Publisher · Free full text
Cytoreductive surgery with hyperthermic intrathoracic chemotherapy for malignant pleural mesothelioma: a systematic review. A.G. Dawson, K. Kutywayo, S.B. Mohammed, et al. 2023;78(4):409-417. Systematic review PubMed · Publisher

Abstract

Introduction: Cytoreductive surgery has been used a part of multimodality treatment in patients with malignant pleural mesothelioma (MPM). The residual microscopic disease that remains will lead to disease progression in the majority of patients. Delivery of hyperthermic intrathoracic chemotherapy at the time of surgery has been used to address this microscopic disease, however it's effect and place in the multimodality treatment sphere is unknown. The aim of this systematic review was to assess the effect of surgery and hyperthermic intrathoracic chemotherapy in patients with MPM on overall survival and disease-free interval.

Methods: Ovid MEDLINE, Embase, Web of Science and the Cochrane Database of Systematic Reviews were searched from database inception through to June 2021. Studies reporting overall survival and/or disease-free interval in patients with MPM undergoing cytoreductive surgery with hyperthermic intrathoracic chemotherapy were considered. Study quality was assessed using the Newcastle-Ottawa Scale. A narrative review was performed.

Results: Fifteen studies were eligible for inclusion comprising 598 patients. Surgery with hyperthermic intrathoracic chemotherapy was associated with a median overall survival and disease-free interval ranging from 11 to 75 months and 7.2 to 57 months, respectively. These appeared to be superior to patients not receiving hyperthermic intrathoracic chemotherapy (overall survival: 5-36 months and disease-free interval: 12.1-21 months). A higher dose of hyperthermic intrathoracic chemotherapy was associated with an improvement in overall survival compared with a lower dose: 18-31 months versus 6-18 months, respectively. The most common morbidity was atrial fibrillation followed by renal complications.

Conclusion: Surgery with hyperthermic intrathoracic chemotherapy offers a safe and effective therapy with an improvement in disease-free interval and overall survival, particularly when hyperthermic intrathoracic chemotherapy is administered at a higher dose.

Prospero Registration Number: CRD42019129002.

© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.
Rate advancement measurement for lung cancer and pleural mesothelioma in asbestos-exposed workers. D. Azzolina, D. Consonni, D. Ferrante, et al. 2023;78(8):808-815. PubMed · Publisher

Abstract

Introduction: Exposure to asbestos increases the risk of lung cancer and mesothelioma. Few studies quantified the premature occurrence of these diseases in asbestos-exposed workers. Focus on premature disease onset (rate advancement or acceleration) can be useful in risk communication and for the evaluation of exposure impact. We estimated rate advancement for total mortality, lung cancer and pleural mesothelioma deaths, by classes of cumulative asbestos exposure in a pooled cohort of asbestos cement (AC) workers in Italy.

Method: The cohort study included 12 578 workers from 21 cohorts, with 6626 deaths in total, 858 deaths from lung cancer and 394 from pleural malignant neoplasm (MN). Rate advancement was estimated by fitting a competitive mortality Weibull model to the hazard of death over time since first exposure (TSFE).

Result: Acceleration time (AT) was estimated at different TSFE values. The highest level of cumulative exposure compared with the lowest, for pleural MN AT was 16.9 (95% CI 14.9 to 19.2) and 33.8 (95% CI 29.8 to 38.4) years at TSFE of 20 and 40 years, respectively. For lung cancer, it was 13.3 (95% CI 12.0 to 14.7) and 26.6 (95% CI 23.9 to 29.4) years, respectively. As for total mortality, AT was 3.35 (95% CI 2.98 to 3.71) years at 20 years TSFE, and 6.70 (95% CI 5.95 to 7.41) at 40 years TSFE.

Conclusion: The current study observed marked rate advancement after asbestos exposure for lung cancer and pleural mesothelioma, as well as for total mortality.

© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.
Fully automated volumetric measurement of malignant pleural mesothelioma by deep learning AI: validation and comparison with modified RECIST response criteria. A.C. Kidd, O. Anderson, G.W. Cowell, et al. 2022;77(12):1251-1259. PubMed · Publisher · Free full text

Abstract

Background: In malignant pleural mesothelioma (MPM), complex tumour morphology results in inconsistent radiological response assessment. Promising volumetric methods require automation to be practical. We developed a fully automated Convolutional Neural Network (CNN) for this purpose, performed blinded validation and compared CNN and human response classification and survival prediction in patients treated with chemotherapy.

Methods: In a multicentre retrospective cohort study; 183 CT datasets were split into training and internal validation (123 datasets (80 fully annotated); 108 patients; 1 centre) and external validation (60 datasets (all fully annotated); 30 patients; 3 centres). Detailed manual annotations were used to train the CNN, which used two-dimensional U-Net architecture. CNN performance was evaluated using correlation, Bland-Altman and Dice agreement. Volumetric response/progression were defined as ≤30%/≥20% change and compared with modified Response Evaluation Criteria In Solid Tumours (mRECIST) by Cohen's kappa. Survival was assessed using Kaplan-Meier methodology.

Results: Human and artificial intelligence (AI) volumes were strongly correlated (validation set r=0.851, p<0.0001). Agreement was strong (validation set mean bias +31 cm3 (p=0.182), 95% limits 345 to +407 cm3). Infrequent AI segmentation errors (4/60 validation cases) were associated with fissural tumour, contralateral pleural thickening and adjacent atelectasis. Human and AI volumetric responses agreed in 20/30 (67%) validation cases κ=0.439 (0.178 to 0.700). AI and mRECIST agreed in 16/30 (55%) validation cases κ=0.284 (0.026 to 0.543). Higher baseline tumour volume was associated with shorter survival.

Conclusion: We have developed and validated the first fully automated CNN for volumetric MPM segmentation. CNN performance may be further improved by enriching future training sets with morphologically challenging features. Volumetric response thresholds require further calibration in future studies.

© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
Incidence, treatment and survival of malignant pleural and peritoneal mesothelioma: a population-based study. J.P. van Kooten, R.A. Belderbos, J.H. von der Thüsen, et al. 2022;77(12):1260-1267. PubMed · Publisher · Free full text

Abstract

Introduction: Malignant mesothelioma (MM) is an aggressive cancer that primarily arises from the pleura (MPM) or peritoneum (MPeM), mostly due to asbestos exposure. This study reviewed the Dutch population-based incidence, treatment and survival since the national ban on asbestos in 1993.

Materials And Methods: Patients with MPM or MPeM diagnosed from 1993 to 2018 were selected from the Dutch cancer registry. Annual percentage change (APC) was calculated for (age-specific and sex-specific) revised European standardised incidence rates (RESR). Treatment pattern and Kaplan-Meier overall survival analyses were performed.

Results: In total, 12 168 patients were included in the study. For male patients younger than 80 years, the MM incidence significantly decreased in the last decade (APC ranging between -9.4% and -1.8%, p<0.01). Among both male and female patients aged over 80 years, the incidence significantly increased during the entire study period (APC 3.3% and 4.6%, respectively, p<0.01). From 2003 onwards, the use of systemic chemotherapy increased especially for MPM (from 9.3% to 39.4%). Overall, 62.2% of patients received no antitumour treatment. The most common reasons for not undergoing antitumour treatment were patient preference (42%) and performance status (25.6%). The median overall survival improved from 7.3 (1993-2003) to 8.9 (2004-2011) and 9.3 months from 2012 to 2018 (p<0.001).

Conclusion: The peak of MM incidence was reached around 2010 in the Netherlands, and currently the incidence is declining in most age groups. The use of systemic chemotherapy increased from 2003, which likely resulted in improved overall survival over time. The majority of patients do not receive treatment though and prognosis is still poor.

© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
Mesothelioma among vehicle mechanics: a controversy?. P.A. Hessel. 2022;77(5):426-427. Editorial · Comment PubMed · Publisher
Risk of asbestosis, mesothelioma, other lung disease or death among motor vehicle mechanics: a 45-year Danish cohort study. R.W. Thomsen, A.H. Riis, E.M. Flachs, et al. 2022;77(5):477-485. PubMed · Publisher

Abstract

Introduction: The risk of asbestosis, malignant mesothelioma and lung cancer among motor vehicle mechanics is of concern because of potential exposure to chrysotile asbestos during brake, clutch and gasket repair and maintenance. Asbestos has also been used in insulation and exhaust systems.

Methods: We examined the long-term risk of incident mesothelioma, lung cancer, asbestosis and other lung diseases and mortality due to mesothelioma, lung cancer, asbestosis and other lung diseases in a nationwide cohort of all men registered as motor vehicle mechanics since 1970 in Denmark. This was compared with the corresponding risk in a cohort of male workers matched 10:1 by age and calendar year, with similar socioeconomic status (instrument makers, dairymen, upholsterers, glaziers, butchers, bakers, drivers, farmers and workers in the food industry, trade or public services).

Results: Our study included 138 559 motor vehicle mechanics (median age 24 years; median follow-up 20 years (maximum 45 years)) and 1 385 590 comparison workers (median age 25 years; median follow-up 19 years (maximum 45 years)). Compared with other workers, vehicle mechanics had a lower risk of morbidity due to mesothelioma/pleural cancer (n=47 cases) (age-adjusted and calendar-year-adjusted HR=0.74 (95% CI 0.55 to 0.99)), a slightly increased risk of lung cancer (HR=1.09 (95% CI 1.03 to 1.14)), increased risk of asbestosis (HR=1.50 (95% CI 1.10 to 2.03)) and a chronic obstructive pulmonary disease risk close to unity (HR=1.02 (95% CI 0.99 to 1.05)). Corresponding HRs for mortality were 0.86 (95% CI 0.64 to 1.15) for mesothelioma/pleural cancer, 1.06 (95% CI 1.01 to 1.12) for lung cancer, 1.79 (95% CI 1.10 to 2.92) for asbestosis, 1.06 (95% CI 0.86 to 1.30) for other lung diseases caused by external agents and 1.00 (95% CI 0.98 to 1.01) for death due to all causes.

Conclusions: We found that the risk of asbestosis was increased among vehicle mechanics. The risk of malignant mesothelioma/pleural cancers was not increased among vehicle mechanics.

© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.
Role of unfolded proteins in lung disease. K.L. Bradley, C.A. Stokes, S.J. Marciniak, et al. 2021;76(1):92-99. Review PubMed · Publisher · Free full text

Abstract

The lungs are exposed to a range of environmental toxins (including cigarette smoke, air pollution, asbestos) and pathogens (bacterial, viral and fungal), and most respiratory diseases are associated with local or systemic hypoxia. All of these adverse factors can trigger endoplasmic reticulum (ER) stress. The ER is a key intracellular site for synthesis of secretory and membrane proteins, regulating their folding, assembly into complexes, transport and degradation. Accumulation of misfolded proteins within the lumen results in ER stress, which activates the unfolded protein response (UPR). Effectors of the UPR temporarily reduce protein synthesis, while enhancing degradation of misfolded proteins and increasing the folding capacity of the ER. If successful, homeostasis is restored and protein synthesis resumes, but if ER stress persists, cell death pathways are activated. ER stress and the resulting UPR occur in a range of pulmonary insults and the outcome plays an important role in many respiratory diseases. The UPR is triggered in the airway of patients with several respiratory diseases and in corresponding experimental models. ER stress has been implicated in the initiation and progression of pulmonary fibrosis, and evidence is accumulating suggesting that ER stress occurs in obstructive lung diseases (particularly in asthma), in pulmonary infections (some viral infections and in the setting of the cystic fibrosis airway) and in lung cancer. While a number of small molecule inhibitors have been used to interrogate the role of the UPR in disease models, many of these tools have complex and off-target effects, hence additional evidence (eg, from genetic manipulation) may be required to support conclusions based on the impact of such pharmacological agents. Aberrant activation of the UPR may be linked to disease pathogenesis and progression, but at present, our understanding of the context-specific and disease-specific mechanisms linking these processes is incomplete. Despite this, the ability of the UPR to defend against ER stress and influence a range of respiratory diseases is becoming increasingly evident, and the UPR is therefore attracting attention as a prospective target for therapeutic intervention strategies.

© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
Use of preclinical models for malignant pleural mesothelioma. M. Shamseddin, J. Obacz, M.J. Garnett, et al. 2021;76(11):1154-1162. Review PubMed · Publisher · Free full text

Abstract

Malignant pleural mesothelioma (MPM) is an aggressive cancer most commonly caused by prior exposure to asbestos. Median survival is 12-18 months, since surgery is ineffective and chemotherapy offers minimal benefit. Preclinical models that faithfully recapitulate the genomic and histopathological features of cancer are critical for the development of new treatments. The most commonly used models of MPM are two-dimensional cell lines established from primary tumours or pleural fluid. While these have provided some important insights into MPM biology, these cell models have significant limitations. In order to address some of these limitations, spheroids and microfluidic chips have more recently been used to investigate the role of the three-dimensional environment in MPM. Efforts have also been made to develop animal models of MPM, including asbestos-induced murine tumour models, MPM-prone genetically modified mice and patient-derived xenografts. Here, we discuss the available in vitro and in vivo models of MPM and highlight their strengths and limitations. We discuss how newer technologies, such as the tumour-derived organoids, might allow us to address the limitations of existing models and aid in the identification of effective treatments for this challenging-to-treat disease.

© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.
Increasing incidence of asbestosis worldwide, 1990-2017: results from the Global Burden of Disease study 2017. M. Yang, D. Wang, S. Gan, et al. 2020;75(9):798-800. PubMed · Publisher

Abstract

Global incidence and temporal trends of asbestosis are rarely explored. Using the detailed information on asbestosis from the Global Burden of Disease (GBD) 2017, we described the age-standardised incidence rate (ASIR) and its average annual percentage change. A Joinpoint Regression model was applied to identify varying temporal trends over time. Although the use of asbestos has been completely banned in many countries, the ASIR of asbestosis increased globally from 1990 to 2017. Furthermore, the most pronounced increases in ASIR of asbestosis were detected in high-income North America and Australasia. These findings indicate that efforts to change the asbestos regulation policy are urgently needed.

© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.
Occupational and environmental risk factors for idiopathic pulmonary fibrosis in Australia: case-control study. M.J. Abramson, T. Murambadoro, S.M. Alif, et al. 2020;75(10):864-869. PubMed · Publisher

Abstract

Introduction: Idiopathic pulmonary fibrosis (IPF) is a lung disease of unknown cause characterised by progressive scarring, with limited effective treatment and a median survival of only 2-3 years. Our aim was to identify potential occupational and environmental exposures associated with IPF in Australia.

Methods: Cases were recruited by the Australian IPF registry. Population-based controls were recruited by random digit dialling, frequency matched on age, sex and state. Participants completed a questionnaire on demographics, smoking, family history, environmental and occupational exposures. Occupational exposure assessment was undertaken with the Finnish Job Exposure Matrix and Australian asbestos JEM. Multivariable logistic regression was used to describe associations with IPF as ORs and 95% CIs, adjusted for age, sex, state and smoking.

Results: We recruited 503 cases (mean±SD age 71±9 years, 69% male) and 902 controls (71±8 years, 69% male). Ever smoking tobacco was associated with increased risk of IPF: OR 2.20 (95% CI 1.74 to 2.79), but ever using marijuana with reduced risk after adjusting for tobacco: 0.51 (0.33 to 0.78). A family history of pulmonary fibrosis was associated with 12.6-fold (6.52 to 24.2) increased risk of IPF. Occupational exposures to secondhand smoke (OR 2.1; 1.2 to 3.7), respirable dust (OR 1.38; 1.04 to 1.82) and asbestos (OR 1.57; 1.15 to 2.15) were independently associated with increased risk of IPF. However occupational exposures to other specific organic, mineral or metal dusts were not associated with IPF.

Conclusion: The burden of IPF could be reduced by intensified tobacco control, occupational dust control measures and elimination of asbestos at work.

© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.
Patient-derived malignant pleural mesothelioma cell cultures: a tool to advance biomarker-driven treatments. N.I. Kanellakis, R. Asciak, M.A. Hamid, et al. 2020;75(11):1004-1008. PubMed · Publisher · Free full text

Abstract

Malignant pleural mesothelioma (MPM) is an aggressive cancer, associated with poor prognosis. We assessed the feasibility of patient-derived cell cultures to serve as an ex vivo model of MPM. Patient-derived MPM cell cultures (n=16) exhibited stemness features and reflected intratumour and interpatient heterogeneity. A subset of the cells were subjected to high-throughput drug screening and coculture assays with cancer-specific cytotoxic T cells and showed diverse responses. Some of the biphasic MPM cells were capable of processing and presenting the neoantigen SSX-2 endogenously. In conclusion, patient-derived MPM cell cultures are a promising and faithful ex vivo model of MPM.

© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

2010s

External validation and recalibration of the Brock model to predict probability of cancer in pulmonary nodules using NLST data. A. Winter, D.R. Aberle, W. Hsu. 2019;74(6):551-563. PubMed · Publisher

Abstract

Introduction: We performed an external validation of the Brock model using the National Lung Screening Trial (NLST) data set, following strict guidelines set forth by the Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis statement. We report how external validation results can be interpreted and highlight the role of recalibration and model updating.

Materials And Methods: We assessed model discrimination and calibration using the NLST data set. Adhering to the inclusion/exclusion criteria reported by McWilliams et al, we identified 7879 non-calcified nodules discovered at the baseline low-dose CT screen with 2 years of follow-up. We characterised differences between Pan-Canadian Early Detection of Lung Cancer Study and NLST cohorts. We calculated the slope on the prognostic index and the intercept coefficient by fitting the original Brock model to NLST. We also assessed the impact of model recalibration and the addition of new covariates such as body mass index, smoking status, pack-years and asbestos.

Results: While the area under the curve (AUC) of the model was good, 0.905 (95% CI 0.882 to 0.928), a histogram plot showed that the model poorly differentiated between benign and malignant cases. The calibration plot showed that the model overestimated the probability of cancer. In recalibrating the model, the coefficients for emphysema, spiculation and nodule count were updated. The updated model had an improved calibration and achieved an optimism-corrected AUC of 0.912 (95% CI 0.891 to 0.932). Only pack-year history was found to be significant (p<0.01) among the new covariates evaluated.

Conclusion: While the Brock model achieved a high AUC when validated on the NLST data set, the model benefited from updating and recalibration. Nevertheless, covariates used in the model appear to be insufficient to adequately discriminate malignant cases.

© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.
Palliative care in mesothelioma: Are current services RESPECT-able enough?. N. Kumar, D. Alrifai, I. Psallidas. 2019;74(4):326-327. Editorial · Comment PubMed · Publisher
Paraneoplastic phenomenon in mesothelioma. A.B. Waqar, D. Menzies, M. Casey, et al. 2019;74(7):719-720. Case report PubMed · Publisher

Abstract

A 71-year-old man presented with breathlessness and visual disturbance. On examination of the chest, he had signs suggestive of a right-sided pleural effusion and a neurological examination yielded conjugate vertical gaze palsy. Subsequent investigations revealed pleural thickening and mesothelioma. His anti-Ma2 antibodies were positive indicating a paraneoplastic syndrome as the cause of the vertical gaze palsy.

© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.
Probability of cancer in lung nodules using sequential volumetric screening up to 12 months: the UKLS trial. M.W. Marcus, S.W. Duffy, A. Devaraj, et al. 2019;74(8):761-767. Randomized trial PubMed · Publisher

Abstract

Background: Estimation of the clinical probability of malignancy in patients with pulmonary nodules will facilitate early diagnosis, determine optimum patient management strategies and reduce overall costs.

Methods: Data from the UK Lung Cancer Screening trial were analysed. Multivariable logistic regression models were used to identify independent predictors and to develop a parsimonious model to estimate the probability of lung cancer in lung nodules detected at baseline and at 3-month and 12-month repeat screening.

Results: Of 1994 participants who underwent CT scan, 1013 participants had a total of 5063 lung nodules and 52 (2.6%) of the participants developed lung cancer during a median follow-up of 4 years. Covariates that predict lung cancer in our model included female gender, asthma, bronchitis, asbestos exposure, history of cancer, early and late onset of family history of lung cancer, smoking duration, FVC, nodule type (pure ground-glass and part-solid) and volume as measured by semiautomated volumetry. The final model incorporating all predictors had excellent discrimination: area under the receiver operating characteristic curve (AUC 0.885, 95% CI 0.880 to 0.889). Internal validation suggested that the model will discriminate well when applied to new data (optimism-corrected AUC 0.882, 95% CI 0.848 to 0.907). The risk model had a good calibration (goodness-of-fit χ[8] 8.13, p=0.42).

Conclusions: Our model may be used in estimating the probability of lung cancer in nodules detected at baseline and at 3 months and 12 months from baseline, allowing more efficient stratification of follow-up in population-based lung cancer screening programmes.

Trial Registration Number: 78513845.

© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.
British Thoracic Society Guideline for the investigation and management of malignant pleural mesothelioma. I. Woolhouse, L. Bishop, L. Darlison, et al. 2018;73(Suppl 1):i1-i30. Guideline PubMed · Publisher
Introducing the new BTS guideline: the investigation and management of pleural malignant mesothelioma. I. Woolhouse, N.A. Maskell. 2018;73(3):210-212. Guideline PubMed · Publisher

Summary

This article introduced the British Thoracic Society (BTS) guideline on the investigation and management of malignant pleural mesothelioma (MPM), published as a supplement in the same issue of Thorax. The authors, who co-chaired the guideline development group, noted that 2535 mesothelioma deaths were reported in the UK in 2012 and that median survival was 9.5 months. The guideline followed the NICE-accredited BTS process, which is based on SIGN methodology and adheres to the AGREE instrument. No biomarker diagnosed MPM consistently with sensitivity and specificity above 90%, so biomarkers were not recommended in isolation as a diagnostic test. A raised mesothelin could, however, assist diagnosis in patients not fit for invasive tests. Based on the MesoVATS and MARS trials, the guideline did not recommend VATS partial pleurectomy for fluid control or extrapleural pneumonectomy for disease control, and it recommended offering suitable patients entry into the MARS-2 trial. Patients with good performance status were to be offered first-line cisplatin and pemetrexed. In the MAPS trial, adding bevacizumab lengthened survival (median 18.8 vs 16.1 months), but bevacizumab was not available in the NHS. After the SMART trial (procedure tract metastases 9/102 vs 16/101; P=0.14), routine prophylactic radiotherapy was not recommended. The authors described ongoing trials, including immunotherapy trials, and stated that the next challenge was implementing the recommendations.

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.
The evidence of benefits of exercise training in interstitial lung disease: a randomised controlled trial. L.M. Dowman, C.F. McDonald, C.J. Hill, et al. 2017;72(7):610-619. Randomized trial PubMed · Publisher

Abstract

Background: Uncertainty exists regarding the clinical relevance of exercise training across the range of interstitial lung diseases (ILDs).

Objective: To establish the impact of exercise training in patients with ILDs of differing aetiology and severity.

Methods: 142 participants with ILD (61 idiopathic pulmonary fibrosis (IPF), 22 asbestosis, 23 connective tissue disease-related ILD (CTD-ILD) and 36 with other aetiologies) were randomised to either 8 weeks of supervised exercise training or usual care. Six-minute walk distance (6MWD), Chronic Respiratory Disease Questionnaire (CRDQ), St George Respiratory Questionnaire IPF-specific version (SGRQ-I) and modified Medical Research Council dyspnoea score were measured at baseline, 9 weeks and 6 months.

Measurements And Main Results: Exercise training significantly increased 6MWD (25 m, 95% CI 2 to 47 m) and health-related quality of life (CRDQ and SGRQ-I) in people with ILD. Larger improvements in 6MWD, CRDQ, SGRQ-I and dyspnoea occurred in asbestosis and IPF compared with CTD-ILD, but with few significant differences between subgroups. Benefits declined at 6 months except in CTD-ILD. Lower baseline 6MWD and worse baseline symptoms were associated with greater benefit in 6MWD and symptoms following training. Greater gains were seen in those whose exercise prescription was successfully progressed according to the protocol. At 6 months, sustained improvements in 6MWD and symptoms were associated with better baseline lung function and less pulmonary hypertension.

Conclusions: Exercise training is effective in patients across the range of ILDs, with clinically meaningful benefits in asbestosis and IPF. Successful exercise progression maximises improvements and sustained treatment effects favour those with milder disease.

Trial Registration Number: Results, ACTRN12611000416998.

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Use of cryobiopsy during pleuroscopy for diagnosis of sarcomatoid malignant mesothelioma. H.P. Chan, M.F. Liew, J.E. Seet, et al. 2017;72(2):193-195. Case report PubMed · Publisher

Summary

Authors from the National University Health System, Singapore, reported the case of a 74-year-old man who presented with a cough of 3 weeks' duration. A chest X-ray showed a large left-sided pleural effusion. The fluid was a lymphocytic exudate with a normal adenosine deaminase level and negative bacterial and mycobacterial cultures. Flex-rigid pleuroscopy showed candle-wax fibrotic parietal pleura. This was sampled with flexible forceps (cusps 2.4 mm when fully open) and with a 2.4 mm cryoprobe using a 4-second freeze time. The pleuroscope and the cryoprobe, with the specimen frozen to its tip, were removed together through the trocar. The cryobiopsies showed sarcomatoid malignant mesothelioma. The forceps biopsies were non-diagnostic, showing fibrin and reactive fibroblasts. The cryobiopsies were larger and deeper, with better-preserved architecture. The authors noted that early or sarcomatoid mesothelioma can be hard to diagnose because the small forceps used through the pleuroscope may not obtain deep enough samples. They noted that surgical approaches have reported diagnostic accuracy of 74–100%. They summarised two earlier small studies of pleural cryobiopsy, in 22 and 15 patients, with diagnostic yields of 95.5% and 93.3%; the complications reported were mainly mild bleeding. The authors concluded that cryobiopsy is not routinely performed during pleuroscopy, but this case highlighted its potential role when smooth, fibrotic pleura is encountered.

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MesobanK UK: an international mesothelioma bioresource. R.C. Rintoul, D.M. Rassl, J. Gittins, et al. 2016;71(4):380-2. PubMed · Publisher · Free full text

Abstract

Malignant pleural mesothelioma causes the greatest societal burden of all the asbestos-related diseases. Progress in better understanding tumour biology will be facilitated by the availability of quality-assured annotated tissue. MesobanK has been created to establish a bioresource of pleural mesothelioma tissue linked to detailed anonymised clinical data. When complete, the bioresource will comprise a 750-patient tissue microarray and prospectively collected tissue, blood and pleural fluid from 300 patients with mesothelioma. Twenty-six new cell lines have also been developed. MesobanK meets all appropriate ethical and regulatory procedures and has recently opened to requests for tissue and data.

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Author's response: Inconsistent results or inconsistent methods? A plea for standardisation of biomarker sampling in mesothelioma studies. J. Creaney, B.W. Robinson. 2015;70(4):374-5. Letter · Comment PubMed · Publisher
Inconsistent results or inconsistent methods? A plea for standardisation of biomarker sampling in mesothelioma studies. K.G. Blyth. 2015;70(4):374. Letter · Comment PubMed · Publisher

Summary

In this letter, the author responded to a Thorax study by Creaney et al on fibulin-3 as a diagnostic marker for malignant pleural mesothelioma (MPM). Their results (plasma area under the curve 0.671, sensitivity 21%) were markedly discordant with those of Pass et al, who used the same assay in a similarly designed study (plasma area under the curve 0.974–0.997, sensitivity 97%). The author argued that Creaney et al had not mentioned one possible confounder: inconsistent timing of biomarker measurements in relation to pleural biopsies, pleurodesis and surgical palliation. He cited studies in other cancers showing effects of biopsy, resection and peritumoural inflammation on biomarker expression. He also cited an earlier study that found a small but statistically significant fall in pleural fluid mesothelin after pleurodesis, with enough variation in paired samples to change the diagnostic classification of 2 of 51 patients. Creaney et al had taken measurements 'within 1 month of diagnosis'. In the Pass study, measurements were made in tertiary surgical centres, which the author considered almost certainly followed extensive pleural intervention. He concluded that such inconsistencies introduce systematic error. He called for standardised timing of biomarker sampling, tested in prospective studies with predefined early sampling, rigorous subsequent diagnostics, and data on confounders such as renal function, body mass index, concomitant drugs and inflammatory indices. He stated that the DIAPHRAGM study in the UK and Ireland was adopting this approach.

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Role of CT in assessing pleural malignancy prior to thoracoscopy. R.J. Hallifax, M. Haris, J.P. Corcoran, et al. 2015;70(2):192-3. PubMed · Publisher

Abstract

The definitive diagnosis of pleural malignancy depends upon histological confirmation by pleural biopsy. CT is reported to have a high sensitivity and specificity for the diagnosis of malignant pleural disease, and is part of the routine diagnostic workup of these patients. The aim of this study was to assess the sensitivity and specificity of CT in detecting pleural malignancy prior to definitive histology obtained via thoracoscopy in a large cohort of patients with suspected malignant pleural disease. Retrospective review of thoracoscopies between January 2008 and January 2013 at two UK tertiary referral centres: Oxford and Preston. The histological results were compared with the CT reported diagnosis before the procedure. CT scan reports were assessed by independent respiratory physicians as to whether the radiologist concluded evidence of malignant pleural disease or benign features only. 211 (57%) of 370 patients included in the analysis had malignant disease: CT scans were reported as 'malignant' in 144, giving a sensitivity of 68% (95% CI 62% to 75%). Of the 159 patients with benign disease, 124 had CT scans reported as benign: specificity 78% (72% to 84%). The positive predictive value of a malignant CT report was 80% (75% to 86%), with a negative predictive value of 65% (58% to 72%). A significant proportion of patients being investigated for malignant disease will have malignancy despite a negative CT report. The use of CT alone in determining which patients should have invasive pleural biopsies should be re-evaluated, and further studies to define the diagnostic pathway are now required.

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Ultrasound-guided pneumothorax induction prior to local anaesthetic thoracoscopy. J.P. Corcoran, I. Psallidas, R.J. Hallifax, et al. 2015;70(9):906-8. PubMed · Publisher

Abstract

Local anaesthetic thoracoscopy (LAT) is performed by a growing number of respiratory physicians in the context of an expanding population with pleural disease. Most LATs occur in patients with moderate to large effusions where the presence of fluid allows safe access to the pleural space. Patients with little or no fluid, but other features concerning for pleural disease, are usually investigated by surgical means. Advanced LAT practitioners can also provide this service through pneumothorax induction, although there is little published data on the safety or efficacy of this technique. We present data from a series of 77 consecutive patients in whom ultrasound-guided pneumothorax induction and LAT were attempted. 67 procedures (87.0%) were successful, with the most common histopathological diagnoses being chronic pleuritis (58.2%) and mesothelioma (16.4%). No adverse events were reported secondary to the procedure. These findings demonstrate the utility of this approach and should inform future practice and guidelines.

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Comparison of fibulin-3 and mesothelin as markers in malignant mesothelioma. J. Creaney, I.M. Dick, T.M. Meniawy, et al. 2014;69(10):895-902. PubMed · Publisher · Free full text

Abstract

Background: Pleural malignant mesothelioma (MM) is a deadly tumour predominantly associated with asbestos exposure. A reliable diagnostic and prognostic marker for MM will significantly enhance clinical care and is an area of intense research. Soluble mesothelin is the most studied and an FDA-approved biomarker for MM. A recent report showed promising results using fibulin-3 as a new diagnostic marker. The aim of this study was to compare the utility of fibulin-3 versus mesothelin, singly or in combination.

Methods: Fibulin-3 and soluble mesothelin were determined by ELISA in the plasma and pleural fluid of 153 patients presenting with a pleural effusion including 82 with MM, 36 with non-MM malignant effusions and 35 with benign effusions. Biomarker concentrations were determined in the plasma of an additional 49 cases with benign asbestos-related disease.

Results: Mesothelin provides better diagnostic accuracy than fibulin-3 for MM whether measured in plasma or pleural effusion: area under the curve (AUC) for plasma was 0.822 (95% CI 0.76 to 0.87) compared with 0.671 (0.61 to 0.73), respectively, and for pleural fluid AUC was 0.815 (0.74 to 0.87) compared with 0.588 (0.51 to 0.67), respectively. Effusion fibulin-3 was an independent significant prognostic factor for survival in MM patients; HR 2.08 (1.14 to 3.82), p=0.017. MM patients with effusion fibulin-3 levels below the median survived significantly longer than those with levels above the median (14.1 vs 7.9 months, p=0.012). Mesothelin and neutrophil to lymphocyte ratio were not significant prognostic markers.

Conclusions: Soluble mesothelin is a superior diagnostic biomarker for MM compared with fibulin-3, whereas fibulin-3 provides superior prognostic information compared with mesothelin.

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Mesothelioma risk after 40 years since first exposure to asbestos: a pooled analysis. A. Reid, N.H. de Klerk, C. Magnani, et al. 2014;69(9):843-50. PubMed · Publisher

Abstract

Background: The risk of malignant mesothelioma (MM) increases proportionally to the cumulative exposure, and to the 3rd or 4th power of time since first exposed, to asbestos. However, little is known about the risk of MM after more than 40 years since first exposure because most epidemiological studies do not have follow-up for sufficient periods of time.

Methods: The data from six cohort studies of exposed workers and two cohorts with residential exposure have been pooled. A nested case control design matched cases and controls on calendar period and age. Conditional logistic regression modelled the relationship between time since first exposure and risk of MM.

Results: The combined data consisted of 22,048 people with asbestos exposure (5769 women), 707 cases of pleural MM (165 in women) and 155 cases of peritoneal MM (32 in women). Median time since first exposure for pleural MM cases was 38.4 years (IQR 31.3-45.3). Median duration of exposure for pleural MM cases was 3.75 years (IQR 0.7-18.2). The rate and risk of pleural MM increased until 45 years following first exposure and then appeared to increase at a slower power of time since first exposure. The rate of increase in peritoneal MM over the 10-50 years since first exposure continued to increase.

Conclusions: Exposure to asbestos confers a long-term risk of developing pleural and peritoneal mesothelioma which increases following cessation of exposure. While the rate of increase appears to start to level out after 40-50 years no one survives long enough for the excess risk to disappear.

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Occupational and non-occupational attributable risk of asbestos exposure for malignant pleural mesothelioma. A. Lacourt, C. Gramond, P. Rolland, et al. 2014;69(6):532-9. PubMed · Publisher

Abstract

Objectives: To estimate the proportion of pleural mesothelioma cases that can be attributed to asbestos exposure in France including non-occupational exposure.

Methods: A population-based case-control study including 437 incident cases and 874 controls was conducted from 1998 to 2002. Occupational and non-occupational asbestos exposure was assessed retrospectively by two expert hygienists. ORs of pleural mesothelioma for asbestos-exposed subjects compared to non-exposed subjects, and population-attributable risk (ARp) of asbestos exposure were estimated using a conditional logistic regression.

Results: A clear dose-response relationship was observed between occupational asbestos exposure and pleural mesothelioma (OR=4.0 (99% CI 1.9 to 8.3) for men exposed at less than 0.1 f/mL-year vs. 67.0 (99% CI 25.6 to 175.1) for men exposed at more than 10 f/mL-year). The occupational asbestos ARp was 83.1% (99% CI 74.5% to 91.7%) for men and 41.7% (99% CI 25.3% to 58.0%) for women. A higher risk of pleural mesothelioma was observed in subjects non-occupationally exposed to asbestos compared to those never exposed. The non-occupational asbestos ARp for these subjects was 20.0% (99% CI -33.5% to 73.5%) in men and 38.7% (99% CI 8.4% to 69.0%) in women. When considering all kinds of asbestos exposure, ARp was 87.3% (99% CI 78.9% to 95.7%) for men and 64.8% (99% CI 45.4% to 84.3%) for women.

Conclusions: Our study suggests that the overall ARp in women is largely driven by non-occupational asbestos exposure arguing for the strong impact of such exposure in pleural mesothelioma occurrence. Considering the difficulty in assessing domestic or environmental asbestos exposure, this could explain the observed difference in ARp between men and women.

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Surgery in the treatment of malignant pleural mesothelioma: recruitment into trials should be the default position. A. Datta, R. Smith, F. Fiorentino, et al. 2014;69(2):194-7. PubMed · Publisher · Free full text

Abstract

Background: Europe is at the peak of an epidemic of malignant pleural mesothelioma and the burden of disease is likely to continue rising in the large areas of the world where asbestos remains unregulated. Patients with mesothelioma present with thoracic symptoms and radiological changes so respiratory physicians take a leading role in diagnosis and management. Belief that the modest survival times reported after radical surgery, whether alone or as part of multimodal therapy, are longer than they it would have been without surgery relies on data from highly selected, uncontrolled, retrospectively analysed case series. The only randomised study, the Mesothelioma and Radical Surgery (MARS) trial showed no benefit. A simple modelling study of registry patients, described here, shows that an impression of longer survival is eroded when patients who were never candidates for operation on grounds of histology, performance status and age are sequentially excluded from the model.

Conclusion: Whenever the question arises `Might an operation help me?' there are two responses that can and should be given. The first is that there is doubt about whether there is any survival or symptomatic benefit from surgery but we know that there is harm. The second is that there are on-going studies, including two randomised trials, which patients should be informed about. The authors suggest that the default position for clinicians should be to encourage recruitment into these trials.
Systemic but not topical TRAIL-expressing mesenchymal stem cells reduce tumour growth in malignant mesothelioma. E.K. Sage, K.K. Kolluri, K. McNulty, et al. 2014;69(7):638-47. PubMed · Publisher · Free full text

Abstract

Malignant pleural mesothelioma is a rare but devastating cancer of the pleural lining with no effective treatment. The tumour is often diffusely spread throughout the chest cavity, making surgical resection difficult, while systemic chemotherapy offers limited benefit. Bone marrow-derived mesenchymal stem cells (MSCs) home to and incorporate into tumour stroma, making them good candidates to deliver anticancer therapies. Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) is a pro-apoptotic molecule that selectively induces apoptosis in cancer cells, leaving healthy cells unaffected. We hypothesised that human MSCs expressing TRAIL (MSCTRAIL) would home to an in vivo model of malignant pleural mesothelioma and reduce tumour growth. Human MSCs transduced with a lentiviral vector encoding TRAIL were shown in vitro to kill multiple malignant mesothelioma cell lines as predicted by sensitivity to recombinant TRAIL (rTRAIL). In vivo MSC homing was delineated using dual fluorescence and bioluminescent imaging, and we observed that higher levels of MSC engraftment occur after intravenous delivery compared with intrapleural delivery of MSCs. Finally, we show that intravenous delivery of MSCTRAIL results in a reduction in malignant pleural mesothelioma tumour growth in vivo via an increase in tumour cell apoptosis.

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Pleurodesis outcome in malignant pleural mesothelioma. E.T. Fysh, S.K. Tan, C.A. Read, et al. 2013;68(6):594-6. PubMed · Publisher

Abstract

Few data exist on the pleurodesis outcome in patients with malignant pleural mesothelioma (MPM). A retrospective review of the Western Australian Mesothelioma Registry over 5 years revealed 390 evaluable patients. Only a subset of patients (42.3%) underwent pleurodesis, surgically (n=78) or by bedside instillation of sclerosants (n=87). Surgical pleurodesis showed no advantages over bedside pleurodesis in efficacy (32% vs 31% failures requiring further drainage, p=0.98), patient survival (p=0.52) or total time spent in hospital from procedure till death (p=0.36). No clinical, biochemical or radiographic parameters tested adequately predict pleurodesis outcome.
A 37-year observation of mortality in Chinese chrysotile asbestos workers. X. Wang, E. Yano, H. Qiu, et al. 2012;67(2):106-10. PubMed · Publisher

Abstract

Objectives: This 37-year prospective cohort study was undertaken to provide additional evidence for mortality risks associated with exposure to chrysotile asbestos.

Methods: 577 asbestos workers and 435 control workers in original cohorts were followed from 1972 to 2008, achieving a follow-up rate of 99% and 73%, respectively. Morality rates were determined based on person-years of observation. Cox proportional hazard models were constructed to estimate HRs of cause-specific mortality, while taking into account age, smoking and asbestos exposure level.

Results: There were 259 (45%) deaths identified in the asbestos cohort, and 96 died of all cancers. Lung cancer (n=53) and non-malignant respiratory diseases (n=81) were major cause-specific deaths, in contrast to nine lung cancers and 11 respiratory diseases in the controls. Age and smoking-adjusted HRs for mortality by all causes and all cancers in asbestos workers were 2.05 (95% CI 1.56 to 2.68) and 1.89 (1.25 to 2.87), respectively. The risks for lung cancer and respiratory disease deaths in asbestos workers were over threefold that in the controls (HR 3.31(95% CI 1.60 to 6.87); HR 3.23 (95% CI 1.68 to 6.22), respectively). There was a clear exposure-response trend with asbestos exposure level and lung cancer mortality in both smokers and non-smokers.

Conclusion: Data from this prospective cohort provide strong evidence for increased mortality risks, particularly from lung cancer and non-malignant respiratory diseases, associated with exposure to chrysotile asbestos, while taking into account of the smoking effect.
The asbestos disease epidemic: here today, here tomorrow. P. Cullinan, N. Pearce. 2012;67(2):98-9. Editorial · Comment PubMed · Publisher

Summary

In this commissioned editorial, the authors discussed the continuing worldwide use of asbestos and commented on a 37-year retrospective cohort study of employees of the Chongqing asbestos plant in China, published in the same issue of Thorax. They noted that total bans were in place in 52 countries, but that elsewhere production and use continued and even increased. In India, use had doubled in the last decade to about 300 000 tonnes a year. Almost all of the estimated 2 million tonnes mined each year was chrysotile. The Chongqing plant had used only chrysotile from Sichuan mines, and a limited analysis of ore samples in 2000 had not detected tremolite. A reference group of electronics factory workers in the same city was followed for the same period. The study found a more than threefold increase in the risk of death from lung cancer, and from non-malignant respiratory disease, among the asbestos workers after statistical control for smoking. It showed an exposure-response relationship in both non-smokers and smokers, and there were two mesothelioma deaths. The authors noted limitations: the absence of tremolite was unverified, earlier or other exposures were possible, and a quarter of the electronics workers could not be traced. They concluded that the study gave further evidence against the 'amphibole hypothesis'. They also concluded that claims that asbestos is safe if used safely are disingenuous at best, and that the asbestos disease epidemic had not ended but had moved.

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Do asbestos-related pleural plaques on HRCT scans cause restrictive impairment in the absence of pulmonary fibrosis?. B. Clin, C. Paris, J. Ameille, et al. 2011;66(11):985-91. PubMed · Publisher

Abstract

Background: It is uncertain whether isolated pleural plaques cause functional impairment.

Objective: To analyse the relationship between isolated pleural plaques confirmed by CT scanning and lung function in subjects with occupational exposure to asbestos.

Methods: The study population consisted of 2743 subjects presenting with no parenchymal interstitial abnormalities on the high-resolution CT (HRCT) scan. Asbestos exposure was evaluated by calculation of an individual cumulative exposure index (CEI). Each subject underwent pulmonary function tests (PFTs) and HRCT scanning. Variables were adjusted for age, smoking status, body mass index, CEI to asbestos and the centres in which the pulmonary function tests were conducted.

Results: All functional parameters studied were within normal limits for subjects presenting with isolated pleural plaques and for those presenting with no pleuropulmonary abnormalities. However, isolated parietal and/or diaphragmatic pleural plaques were associated with a significant decrease in total lung capacity (TLC) (98.1% predicted in subjects with pleural plaques vs. 101.2% in subjects free of plaques, p=0.0494), forced vital capacity (FVC) (96.6% vs. 100.4%, p<0.001) and forced expiratory volume in 1 s (FEV(1)) (97.9% vs. 101.9%, p=0.0032). In contrast, no significant relationship was observed between pleural plaques and FEV1/FVC ratio, forced expiratory flow at 25-75% FVC and residual volume. A significant correlation was found between the extent of pleural plaques and the reduction in FVC and TLC, whereas plaque thickness was not related to functional impairment.

Conclusions: The results show a relationship between isolated parietal and/or diaphragmatic pleural plaques and a trend towards a restrictive pattern, although the observed decrease in FVC and TLC is unlikely to be of real clinical relevance for the majority of subjects in this series.
Increased mortality from infectious pneumonia after occupational exposure to inorganic dust, metal fumes and chemicals. K. Torén, I. Qvarfordt, I.A. Bergdahl, et al. 2011;66(11):992-6. PubMed · Publisher

Abstract

Objectives: There are epidemiological studies indicating that exposure to metal fumes is a risk factor for infectious pneumonia. Whether occupational exposure to other agents, such as inorganic dust or chemicals, also increases the risk for infectious pneumonia is not clear. The aim of the present study was to elucidate whether occupational exposure to respiratory pollutants and irritants increases the risk for infectious pneumonia.

Design: Prospective cohort study. Setting Swedish male construction workers. Participants 320,143 male construction workers exposed to inorganic dust (asbestos, man-made mineral fibres, dust from cement, concrete and quartz), wood dust, metal fumes and chemicals (organic solvents, diisocyanates and epoxi resins) or unexposed. Main outcome measures The cohort was followed from 1971 to 2003 and the main outcome measures were mortality to infectious pneumonia, lobar pneumonia or pneumococcal pneumonia. RRs were obtained by the person-years method and from Poisson regression models, adjusting for baseline values of age and smoking habits.

Results: Among men aged 20-64 years there was increased mortality from infectious pneumonias among construction workers exposed to metal fumes (RR 2.31, 95% CI 1.35 to 3.95), inorganic dust (RR 1.87, 95% CI 1.22 to 2.87) and chemicals (RR 1.91, 95% CI 1.37 to 3.22). The mortality was also increased from both lobar pneumonia and pneumococcal pneumonia. Among men aged 65-84 years the occupational exposure to inorganic dust and chemicals was associated with slightly increased mortality from infectious pneumonia. Among groups with mutually exclusive exposures there was increased mortality from infectious pneumonias among construction workers exposed to inorganic dust, but not among those exposed to wood dust or chemicals. There were no cases among workers exposed only to metal fumes.

Conclusions: Our findings indicate that exposure to inorganic dust increases the mortality from infectious pneumonias, especially lobar pneumonia and pneumococcal pneumonia. The mechanism is unclear, but the effect may be mediated through induced airways inflammation.
Cryptogenic fibrosing alveolitis and lung cancer: the BTS study. J.M. Harris, I.D. Johnston, R. Rudd, et al. 2010;65(1):70-6. PubMed · Publisher

Abstract

Background: The risk of lung cancer is often reported to be increased for patients with cryptogenic fibrosing alveolitis (CFA).

Methods: Vital status was sought for all 588 members of the British Thoracic Society (BTS) cryptogenic fibrosing alveolitis (CFA) study 11 years after entry to the cohort. Observed deaths due to lung cancer were compared with expected deaths using age-, sex- and period-adjusted national rates. The roles of reported asbestos exposure and smoking were also investigated.

Results: 488 cohort members (83%) had died; 46 (9%) were certified to lung cancer (ICD9 162). The standardised mortality ratio (SMR) was 7.4 (95% CI 5.4 to 9.9). Stratified analysis showed increased lung cancer mortality among younger subjects, men and ever smokers. Using an independent expert panel, 25 cohort members (4%) were considered to have at least moderate exposure to asbestos; the risk of lung cancer was increased for these subjects (SMR 13.1 (95% CI 3.6 to 33.6)) vs 7.2 (95% CI 5.2 to 9.7) for those with less or no asbestos exposure). Ever smoking was reported by 448 (73%) of the cohort and was considerably higher in men than in women (92% vs 49%; p<0.001). Most persons who died from lung cancer were male (87%), and all but two (96%) had ever smoked. Ever smokers presented at a younger age (mean 67 vs 70 years; p<0.001) and with less breathlessness (12% smokers reported no breathlessness vs 5% never smokers; p = 0.02).

Conclusions: These findings confirm an association between CFA and lung cancer although this relationship may not be causal. The high rate of smoking and evidence that smokers present for medical attention earlier than non-smokers suggest that smoking could be confounding this association.

2000s

EGFR and PDGFR differentially promote growth in malignant epithelioid mesothelioma of short and long term survivors. H. Kothmaier, F. Quehenberger, I. Halbwedl, et al. 2008;63(4):345-51. PubMed · Publisher

Abstract

Background: Malignant pleural mesothelioma (MPM) is an asbestos related tumour difficult to detect early and treat effectively. Asbestos causes genetic modifications and cell signalling events that favour the resistance of MPM to apoptosis and chemotherapy. Only a small number of patients, approximately 10%, survive more than 3 years. The aim of our study was to assess possible differences within signalling pathways between short term survivors (survival <3 years; STS) and long term survivors (survival >3 years; LTS) of MPM.

Methods: 37 antibodies detecting proteins engaged in cell signalling pathways, enforcing proliferation, antiapoptosis, angiogenesis and other cellular activities were investigated by tissue microarray (TMA) technology.

Results: Epidermal growth factor receptor (EGFR) was expressed stronger in LTS whereas platelet derived growth factor receptor (PDGFR) signalling was more abundant in STS. Expression of TIE2/Tek, a receptor for tyrosine kinases involved in angiogenesis, was differentially regulated via PDGFR and thus is more important in STS. Antiapoptosis was upregulated in STS by signal transducer and activator of transcription 1 (STAT1)-survivin and related molecules, but not in LTS. Our study provides novel insights into the regulatory mechanisms of signalling pathways in MPM, which differentially promote tumour growth in LTS and STS.

Conclusion: We have demonstrated that small scale proteomics can be carried out by powerful linkage of TMA, immunohistochemistry and statistical methods to identify proteins which might be relevant targets for therapeutic intervention.
Population based epidemiology and prognosis of mesothelioma in Leeds, UK. A. Chapman, S. Mulrennan, B. Ladd, et al. 2008;63(5):435-9. PubMed · Publisher

Abstract

Introduction: Malignant mesothelioma is a fatal neoplasm, which is rapidly increasing in incidence throughout Western Europe. To date there have been no studies reporting on the natural history and interventional practices on a comprehensive unselected population, as opposed to reports from referral institutions or compensation claimants. We present a population based study capturing data on all patients with mesothelioma presenting within a defined geographical area over a 4 year period in the UK.

Method: Data of all cases occurring in Leeds with a population of 750 000 were collected retrospectively from 2002 to 2003 and prospectively from 2004 to 2005. All patients' hospital records and the Trust histology database were reviewed, as well as coroner's reports on all patients with a post mortem diagnosis of mesothelioma.

Results: Over the 4 year study period, there were a total of 146 cases in Leeds; 77% were male. Median age was 74 years (range 36-93). Median survival from diagnosis was 8.9 months. 92% and 8% had histological or cytological confirmation, respectively. 85% had documented evidence of definite or probable exposure to asbestos. 110/146 (75%) had symptomatic pleural effusions at presentation. Twice the number of patients (42 vs 17) were managed with surgical rather than bedside pleurodesis and these had a lower recurrence rate (14% vs 47%; p = 0.02). 122 patients had video assisted thoracoscopic surgery/cutting CT biopsies or chest drains. 73/122 (60%) had prophylactic radiotherapy to these sites. There were seven cases (5%) of tract invasion by tumour and six of these had received prophylactic radiotherapy. Median time to seeding was 174 days. 92/146 (63%) had a performance status of 2 or better at diagnosis but only 54/146 were considered fit for chemotherapy. Of these, 28 (52%) declined chemotherapy; the overall uptake of chemotherapy or entry into a trial was 18%. No patient had radical surgery.

Conclusion: This comprehensive population based audit has shown that the median age at presentation of malignant mesothelioma is increasing and baseline performance status and survival is worse than in selected series. 37% of patients were considered suitable for palliative chemotherapy but less than 20% accepted this offer. Thorascopic pleurodesis appears to be associated with fewer recurrences. The role of prophylactic radiotherapy to chest drain and biopsy sites needs reappraisal.
Syndrome of pleural and retrosternal "bridging" fibrosis and retroperitoneal fibrosis in patients with asbestos exposure. V. Cottin, P.Y. Brillet, F. Combarnous, et al. 2008;63(2):177-9. Case report PubMed · Publisher

Abstract

Two case histories are described of pleural and anterior mediastinal fibrosis presenting as a continuous fibrotic process with thick parietal pleural plaques extending from one pleura to the contralateral pleura through the retrosternal area, and with retroperitoneal fibrosis. Follow-up over 4 years in one case demonstrated rapid progression of disease, with pleural fibrosis preceding retrosternal and retroperitoneal fibrosis. Histopathological analysis in both cases showed non-tumoral fibrosis with broad fibrous bundles surrounding fibroblasts (and lymphocytes in one case). Possible causes such as infections and exposure to ergot derivatives were excluded. Both patients had been slightly or moderately exposed to asbestos. These cases represent an unusual new presentation of pleural and retrosternal fibrosis extending beyond the anatomical structures and associated with retroperitoneal fibrosis.
The epidemiology and treatment of mesothelioma in South East England 1985-2002. V. Mak, E. Davies, V. Putcha, et al. 2008;63(2):160-6. PubMed · Publisher

Abstract

Objectives: To describe trends in the incidence of mesothelioma for men and women in South East England and the geographical variation at the level of primary care trust. To describe treatment patterns by cancer network of residence, and relative survival by cancer network, disease stage and treatment modality.

Methods: 5753 cases were extracted from the Thames Cancer Registry database. We calculated age standardised incidence rates for each year, age specific incidence rates in 10 year age groups, and we used linear regression to compute the average annual percentage change in age standardised incidence. We used Poisson regression to analyse generational trends in incidence.

Results: Men had five times higher incidence of mesothelioma than women. In men, there was an overall 4% increase per year between 1985 and 2002. Over the same period, the overall increase in incidence for women was 5% per year. The incidence was highest in men aged over 70 years, and men aged over 80 years had the highest increase of 8% per year. The incidence rate ratio increased for men born between 1892 and 1942 and started to slow for those born from 1947 onwards. Areas along the Thames and its estuary had the highest incidence. There was some variation by cancer network in the proportion of patients receiving cancer surgery, radiotherapy and chemotherapy. There were no discernable differences in relative survival by cancer network of residence or disease stage but those receiving combined treatment had higher 5 year survival.

Conclusions: Mesothelioma incidence has increased in South East England, particularly for men aged over 70 years. The highest incidence occurs along the Thames and its estuary, reflecting areas of asbestos use in shipbuilding and industry in the past. More research is needed to understand the interrelationships of prognostic factors, treatment choices and survival, and to determine the best care and support for these patients and their families.
Autofluorescence bronchoscopy for lung cancer surveillance based on risk assessment. G. Loewen, N. Natarajan, D. Tan, et al. 2007;62(4):335-40. PubMed · Publisher · Free full text

Abstract

Background: This is a preliminary report of an ongoing prospective bimodality lung cancer surveillance trial for high-risk patients. Bimodality surveillance incorporates autofluorescence bronchoscopy (AFB) and spiral CT (SCT) scanning in high-risk patients as a primary lung cancer surveillance strategy, based entirely on risk factors. AFB was used for surveillance and findings were compared with conventional sputum cytology for the detection of malignancy and pre-malignant central airway lesions.

Methods: 402 patients registering at Roswell Park Cancer Institute were evaluated with spirometric testing, chest radiography, history and physical examination, of which 207 were deemed eligible for the study. For eligibility, patients were required to have at least two of the following risk factors: (1) > or =20 pack year history of tobacco use, (2) asbestos-related lung disease on the chest radiograph, (3) chronic obstructive pulmonary disease with a forced expiratory volume in 1 s (FEV(1)) <70% of predicted, and (4) prior aerodigestive cancer treated with curative intent, with no evidence of disease for >2 years. All eligible patients underwent AFB, a low-dose SCT scan of the chest without contrast, and a sputum sample was collected for cytological examination. Bronchoscopic biopsy findings were correlated with sputum cytology results, SCT-detected pulmonary nodules and surveillance-detected cancers. To date, 186 have been enrolled with 169 completing the surveillance procedures.

Results: Thirteen lung cancers (7%) were detected in the 169 subjects who have completed all three surveillance studies to date. Pre-malignant changes were common and 66% of patients had squamous metaplasia or worse. Conventional sputum cytology missed 100% of the dysplasias and 68% of the metaplasias detected by AFB, and failed to detect any cases of carcinoma or carcinoma-in-situ in this patient cohort. Sputum cytology exhibited 33% sensitivity and 64% specificity for the presence of metaplasia. Seven of 13 lung cancers (58%) were stage Ia or less, including three patients with squamous cell carcinoma. Patients with peripheral pulmonary nodules identified by SCT scanning of the chest were 3.16 times more likely to exhibit pre-malignant changes on AFB (p<0.001).

Conclusion: Bimodality surveillance will detect central lung cancer and pre-malignancy in patients with multiple lung cancer risk factors, even when conventional sputum cytology is negative. AFB should be considered in high-risk patients, regardless of sputum cytology findings.
BTS statement on malignant mesothelioma in the UK, 2007. British Thoracic Society Standards of Care Committee. 2007;62 Suppl 2(Suppl 2):ii1-ii19. Consensus statement PubMed · Publisher · Free full text
Increased alveolar nitric oxide concentration and high levels of leukotriene B(4) and 8-isoprostane in exhaled breath condensate in patients with asbestosis. H. Lehtonen, P. Oksa, L. Lehtimäki, et al. 2007;62(7):602-7. PubMed · Publisher · Free full text

Abstract

Background: Inhaled asbestos fibres can cause inflammation and fibrosis in the lungs called asbestosis. However, there are no non-invasive means to assess and follow the severity of the inflammation. Exhaled nitric oxide (NO) measured at multiple exhalation flow rates can be used to assess the alveolar NO concentration and bronchial NO flux, which reflect inflammation in the lung parenchyma and airways, respectively. The aim of the present study was to investigate whether exhaled NO or markers in exhaled breath condensate could be used to assess inflammation in asbestosis.

Methods: Exhaled NO and inflammatory markers (leukotriene B(4) and 8-isoprostane) in exhaled breath condensate were measured in 15 non-smoking patients with asbestosis and in 15 healthy controls. Exhaled NO concentrations were measured at four constant exhalation flow rates (50, 100, 200 and 300 ml/s) and alveolar NO concentration and bronchial NO flux were calculated according to the linear model of pulmonary NO dynamics.

Results: The mean (SE) alveolar NO concentration was significantly higher in patients with asbestosis than in controls (3.2 (0.4) vs 2.0 (0.2) ppb, p = 0.008). There was no difference in bronchial NO flux (0.9 (0.1) vs 0.9 (0.1) nl/s, p = 0.93) or NO concentration measured at ATS standard flow rate of 50 ml/s (20.0 (2.0) vs 19.7 (1.8) ppb, p = 0.89). Patients with asbestosis had increased levels of leukotriene B4 (39.5 (6.0) vs 15.4 (2.9) pg/ml, p = 0.002) and 8-isoprostane (33.5 (9.6) vs 11.9 (2.8) pg/ml, p = 0.048) in exhaled breath condensate and raised serum levels of C-reactive protein (2.3 (0.3) vs 1.1 (0.2) mug/ml, p = 0.003), interleukin-6 (3.5 (0.5) vs 1.7 (0.4) pg/ml, p = 0.007) and myeloperoxidase (356 (48) vs 240 (20) ng/ml, p = 0.034) compared with healthy controls.

Conclusions: Patients with asbestosis have an increased alveolar NO concentration and high levels of leukotriene B4 and 8-isoprostane in exhaled breath. Measurement of exhaled NO at multiple exhalation flow rates and analysis of inflammatory markers in exhaled breath condensate are promising non-invasive means for assessing inflammation in patients with asbestosis.
Mesothelioma after lung transplantation. P.N. Chhajed, L. Bubendorf, H. Hirsch, et al. 2006;61(10):916-7. Case report PubMed · Publisher · Free full text

Abstract

The case history is presented of a lung transplant recipient who developed malignant mesothelioma. This is thought to be the first such report. Mesothelioma should be suspected in lung transplant recipients with a haemorrhagic pleural effusion in the native lung when there is no convincing evidence for bronchogenic carcinoma or post transplant lymphoproliferative disease, even in the absence of exposure to asbestos.
Asbestos, asbestosis, and lung cancer: a critical assessment of the epidemiological evidence. P.A. Hessel, J.F. Gamble, J.C. McDonald. 2005;60(5):433-6. Review PubMed · Publisher · Free full text

Abstract

The question of whether lung cancer can be attributed to asbestos exposure in the absence of asbestosis remains controversial. Nine key epidemiological papers are reviewed in a point/counterpoint format, giving the main strengths and limitations of the evidence presented. Of the nine papers, two concluded that asbestosis was necessary and seven that it was not. However, the study design, nature and circumstances of exposure and method of analysis of the studies differed considerably, and none was considered definitive. It is concluded that, because of the relative insensitivity of chest radiography and the uncertain specificity of findings from histological examinations or computed tomography, it is unlikely that epidemiology alone can put either the strict scientific or practical medicolegal questions beyond doubt. It is probable that the issue may depend critically on asbestos fibre type, an aspect not so far addressed.
Effects of asbestos and smoking on the levels and rates of change of lung function in a crocidolite exposed cohort in Western Australia. H.S. Alfonso, L. Fritschi, N.H. de Klerk, et al. 2004;59(12):1052-6. PubMed · Publisher · Free full text

Abstract

Background: Increased rates of death from asbestos related diseases have been reported in former workers and residents exposed to crocidolite (blue asbestos) at Wittenoom, Western Australia. Exposure to asbestos is associated with reduced static lung volumes, gas transfer and lung compliance, and a restrictive ventilatory abnormality.

Methods: The effects of crocidolite exposure and smoking history on levels and rates of change of lung function were evaluated using a linear mixed model. Lung function was measured as forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and FEV1/FVC.

Results: Cumulative doses of asbestos and the presence of radiographic asbestosis were associated with lower levels of FEV1 and FVC and a steeper decline during the period of observation. Subjects exposed to asbestos at a younger age had lower levels of FEV1 and FVC. Current smokers had lower levels and a steeper decline in lung function than never smokers. No significant interactions between crocidolite exposure and smoking on the levels or rates of change of lung function were found.

Conclusions: The deleterious effects of crocidolite exposure on lung function persist in this population, despite asbestos exposure having ceased more than 30 years ago. No significant interactions were found in this population between asbestos and smoking at the first visit or longitudinally.
Primary pleural lymphomas. H. Ahmad, J. Pawade, S. Falk, et al. 2003;58(10):908-9. Case report PubMed · Publisher · Free full text

Abstract

Two patients are presented with primary low grade pleural B cell lymphomas with no history of a pyothorax.
Expression of p21 in SV40 large T antigen positive human pleural mesothelioma: relationship with survival. A. Baldi, A.M. Groeger, V. Esposito, et al. 2002;57(4):353-6. PubMed · Publisher · Free full text

Abstract

Background: Mesothelioma is the most commonly occurring primary pleural neoplasm. Several studies have documented an increase in the incidence of this malignancy during the last decades. Although the association between asbestos exposure and development of mesothelioma is generally accepted, the exact mechanism of carcinogenesis is unknown. Recently, Simian virus 40 large T antigen (SV40 Tag) expression has been detected in pleural mesothelioma. The ability of SV40 oncoproteins to inactivate p53 and retinoblastoma tumour suppressor proteins has been proposed as an important step in the pathogenesis of human mesothelioma.

Methods: To obtain a better understanding of the molecular mechanisms of the pathogenesis of mesothelioma, the expression of the cell cycle inhibitor p21(WAF1/CIP1) (p21), a downstream target of p53, was evaluated immunohistochemically in a group of 29 mesothelioma specimens already characterised for the presence of SV40 Tag sequences.

Results: Statistical analysis did not reveal any correlation between p21 expression and histopathological type of mesothelioma using the kappa(2) test (p=0.577). A significant positive relationship was found between p21 expression level and the patients' overall survival according to the Kaplan-Meier survival curves and using a log rank test (median difference in survival 7 months, 95% CI 4.8 to 9.9; p<0.001).

Conclusions: Determination of p21 expression bears a prognostic significance in patients affected with mesothelioma, further underlining the role of SV40 in the pathogenesis of malignant pleural mesothelioma.
Mesothelioma. R. Rudd, J. Moore-Gillon, M. Muers. 2002;57(2):187. Letter PubMed · Publisher · Free full text
One fibre or many; what causes mesothelioma?. A. Seaton. 2002;57(2):186-7. Case report · Letter PubMed · Publisher · Free full text
Statement on malignant mesothelioma in the UK. M. Robinson, J. Wiggins. 2002;57(2):187. Letter · Comment PubMed · Publisher · Free full text

Summary

This letter to the editor added material to Appendix 3, "Sources of information and help available for patients and carers", of the British Thoracic Society statement on malignant mesothelioma in the United Kingdom, published in Thorax in 2001 (56:250–65). The authors, from the Mesothelioma Information Service at Cookridge Hospital, Leeds, and from Wexham Park Hospital, Slough, listed Asbestos Support Groups that they described as the major practical sources of information in the UK for people with asbestos related diseases. They stated that most of these groups provided a drop-in and telephone service giving confidential free advice and support to patients and families, and that the groups had particular expertise in industrial injury benefits and in government and civil compensation claims. The letter gave telephone numbers for groups in Manchester, Sheffield, Liverpool, Bradford, West Yorkshire, Cheshire and Nottingham, and, in Scotland, for Clydeside Action on Asbestos and the Clydebank Asbestos Group. The authors noted that although most of the groups were in the north of England, they accepted telephone queries from any part of Great Britain. They also named the Macmillan Mesothelioma Information Line and the Occupational and Environmental Diseases Association (OEDA) as other important sources of help and information. Both had been mentioned in the original statement.

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Statement on malignant mesothelioma in the United Kingdom. British Thoracic Society Standards of Care Committee. 2001;56(4):250-65. Consensus statement · Review PubMed · Publisher · Free full text
Summary

The British Thoracic Society (BTS) Standards of Care Committee was asked by the National Health Executive in England to consider how the management of malignant mesothelioma could be improved, given its increasing incidence. A Working Party of clinicians, supplemented by co-opted radiologists, pathologists and oncologists, compiled guidance on pleural and peritoneal mesothelioma in the UK. The guidance was based on literature searches and reviews. The draft was reviewed by BTS members, expert groups, and representatives of patients and the government. The authors stated that it was not strictly evidence based and was offered for guidance.

The statement noted that mesothelioma is almost always caused by inhalation of asbestos fibre many years before presentation. Cases in Britain were expected to rise from about 1300 to more than 3000 a year. All types of asbestos can cause the disease, and one series reported a mean latency of 41 years.

The statement covered:
- presentation and prognosis, with median survival of 8 to 14 months;
- diagnosis, stressing a detailed occupational history and CT scanning;
- pathology and staging;
- radical surgery and management of pleural effusions;
- radiotherapy, chemotherapy and new treatments;
- palliative care and peritoneal mesothelioma.
It recommended specialist care and chemotherapy preferably within clinical trials. It also described UK benefit and compensation routes, including Industrial Injuries Disablement Benefit and common law claims.

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Malignant mesothelioma: predictors of prognosis and clinical trials. J.P. Steele, R.M. Rudd. 2000;55(9):725-6. Comment · Editorial PubMed · Publisher · Free full text

Summary

In this editorial, the authors discussed prognosis and clinical trials in malignant mesothelioma, commenting on a study by Edwards et al in the same issue of Thorax. They noted that the incidence of malignant mesothelioma was increasing in the UK and continental Europe and that effective treatment remained elusive. Radical surgery was rarely performed in the UK. Radiotherapy could relieve pain but had no evidence of improving survival. Three recent phase II chemotherapy trials had reported tumour response rates exceeding 20%, with improved symptoms. The authors reviewed staging systems (Butchart, IMIG and Brigham). They argued that prognostic scoring systems were the most practical way to assess prognosis for most patients and to stratify patients in randomised trials. They summarised Edwards et al's retrospective analysis of patients treated at a single institution in Leicester between 1988 and 1999. That analysis found that the EORTC and CALGB scoring systems both correctly identified patients with a poor prognosis. On multivariate analysis, poor prognostic factors were sarcomatous cell type, low haemoglobin, high white blood cell count, poor performance status and male sex. One and two year survival rates were 21.3% and 3.5%. The authors concluded that these systems could be considered for prospective use in forthcoming phase II and III trials. They also described a planned British Thoracic Society and Medical Research Council three arm phase III trial comparing vinorelbine, MVP chemotherapy and best supportive care.

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Malignant vascular tumours of the pleura in "asbestos" workers and endothelial differentiation in malignant mesothelioma. R.L. Attanoos, S.K. Suvarna, E. Rhead, et al. 2000;55(10):860-3. Case report PubMed · Publisher · Free full text

Abstract

Background: Three cases of diffuse malignant vascular tumours of the pleura are described which mimicked malignant mesothelioma clinically and pathologically (so called "pseudomesothelioma"). All had occupational histories of exposure to asbestos. The relationship of these tumours to mesothelioma and asbestos exposure is discussed.

Methods: To examine the histogenetic relationship between mesothelioma and these three tumours an immunohistochemical analysis of vascular marker (CD31, CD34, and Von Willebrand factor) expression was undertaken in 92 cases of pleural mesothelioma, in addition to these three tumours. Electron microscopic fibre analysis of lung tissue was performed on each of the three cases to assess asbestos fibre content.

Results: Diffuse pleural epithelioid haemangioendotheliomas may closely resemble malignant mesothelioma clinically and pathologically but, of the 92 pleural mesotheliomas tested, none showed expression of CD31, CD34, and Von Willebrand factor. Although all three cases had claimed exposure to asbestos, ferruginous bodies typical of asbestos were only seen by light microscopy in case 2, and only in this subject was the asbestos fibre content raised in comparison with the range seen in a non-exposed background population. The latent period in the pleural epithelioid haemangioendotheliomas ranged from 18 to 60 years.

Conclusions: Endothelial differentiation does not appear to occur in mesothelioma and therefore should be clearly separated from it. No definite association between pleural epithelioid haemangioendothelioma and exposure to asbestos can be made from this small series but further investigation is warranted.
Prognostic factors for malignant mesothelioma in 142 patients: validation of CALGB and EORTC prognostic scoring systems. J.G. Edwards, K.R. Abrams, J.N. Leverment, et al. 2000;55(9):731-5. PubMed · Publisher · Free full text

Abstract

Background: The incidence of malignant mesothelioma is increasing. There is the perception that survival is worse in the UK than in other countries. However, it is important to compare survival in different series based on accurate prognostic data. The European Organisation for Research and Treatment of Cancer (EORTC) and the Cancer and Leukaemia Group B (CALGB) have recently published prognostic scoring systems. We have assessed the prognostic variables, validated the EORTC and CALGB prognostic groups, and evaluated survival in a series of 142 patients.

Methods: Case notes of 142 consecutive patients presenting in Leicester since 1988 were reviewed. Univariate analysis of prognostic variables was performed using a Cox proportional hazards regression model. Statistically significant variables were analysed further in a forward, stepwise multivariate model. EORTC and CALGB prognostic groups were derived, Kaplan-Meier survival curves plotted, and survival rates were calculated from life tables.

Results: Significant poor prognostic factors in univariate analysis included male sex, older age, weight loss, chest pain, poor performance status, low haemoglobin, leukocytosis, thrombocytosis, and non-epithelial cell type (p<0.05). The prognostic significance of cell type, haemoglobin, white cell count, performance status, and sex were retained in the multivariate model. Overall median survival was 5.9 (range 0-34.3) months. One and two year survival rates were 21.3% (95% CI 13.9 to 28.7) and 3. 5% (0 to 8.5), respectively. Median, one, and two year survival data within prognostic groups in Leicester were equivalent to the EORTC and CALGB series. Survival curves were successfully stratified by the prognostic groups.

Conclusions: This study validates the EORTC and CALGB prognostic scoring systems which should be used both in the assessment of survival data of series in different countries and in the stratification of patients into randomised clinical studies.

1990s

The molecular basis of asbestos induced lung injury. D.W. Kamp, S.A. Weitzman. 1999;54(7):638-52. Review PubMed · Publisher · Free full text
Improving surgical resection rate in lung cancer. C. Laroche, F. Wells, R. Coulden, et al. 1998;53(6):445-9. Comment PubMed · Publisher · Free full text

Abstract

Background: Surgical resection is the recognised treatment of choice for patients with stage I or II non-small cell lung cancer (NSCLC). In the UK surgical resection rates have remained far lower (< 10%) than those achieved in Europe and the USA (> 20%), despite the recent introduction of fast access investigation units. It remains unclear therefore why UK surgical resection rates lag so far behind those of other countries.

Methods: A new quick access two stop investigation service was established at Papworth in November 1995 to investigate all patients presenting to any of three surrounding health districts with suspected lung cancer. Once staging was complete, all patients with confirmed lung cancer were reviewed by a multidisciplinary team which included an oncologist and a thoracic surgeon. Time from presentation to definitive treatment and surgical resection rates were reviewed.

Results: Two hundred and nine (76%) of a total of 275 consecutive patients investigated had confirmed lung cancer (28 small cell, 181 non-small cell). Of the remainder, eight patients (2%) had metastatic disease, four (1%) had other thoracic malignancy (thymoma, mesothelioma), four patients (1%) had benign thoracic tumours, and 50 (18%) had other non-malignant diseases. Of the 181 patients with non-small cell primary lung cancer, 47 (25%) underwent successful surgical resection, of whom 59% had stage I and 21% stage II disease. The failed thoracotomy rate was 11%. Median time from presentation at the peripheral clinic to surgical resection was 5 weeks (range 1-13).

Conclusion: Quick access investigation, high histological confirmation rates, routine CT scanning, and review of every patient with confirmed lung cancer by a thoracic surgeon led to a substantial increase in the successful surgical resection rate. These results support the growing concern that many patients with operable tumours are being denied the chance of curative surgery in our present system.
Lump sum compensation for asbestos related lung disease. T. Williams, P. Slade, J. Raeburn. 1998;53(7):535. PubMed · Publisher · Free full text
Telomerase activity in human pleural mesothelioma. K. Dhaene, R. Hübner, S. Kumar-Singh, et al. 1998;53(11):915-8. PubMed · Publisher · Free full text

Abstract

Background: Gradual telomere erosion eventually limits the replicative life span of somatic cells and is regarded as an ultimate tumour suppressor mechanism, eliminating cells that have accumulated genetic alterations. Telomerase, which has been found in over 85% of human cancers, elongates telomeres and may be required for tumorigenesis by the process of immortalisation. Malignant mesothelioma is an incurable malignancy with a poor prognosis. The disease becomes symptomatic decades after exposure to carcinogenic asbestos fibres, suggesting the long term survival of pre-malignant cell clones. This study investigated the presence of telomerase in pleural malignant mesothelioma, which may be the target for future anti-telomerase drugs.

Methods: Telomerase activity was semiquantitatively measured in extracts from 22 primary pleural mesotheliomas, two benign solitary fibrous tumours of the pleura, four mesothelioma cell lines, and six short term mesothelial cell cultures from normal pleura using a non-isotopic dilution assay of the telomeric repeat amplification protocol.

Results: Twenty of the 22 primary mesotheliomas (91%) and all tumour derived mesothelioma cell lines were telomerase positive. Different levels of enzyme activity were observed in the tumours of different histological subtypes. Telomerase activity could not be detected in the six normal mesothelial cell cultures or in the two mesotheliomas. Both benign solitary fibrous tumours showed strong telomerase activity.

Conclusions: Telomerase activity is found in a high proportion of mesotheliomas and anti-telomerase drugs might therefore be useful clinically. The results are consistent with the hypothesis that telomerase activity may be a feature of carcinogenesis in mesotheliomas and possibly in many other cancers.
Asbestos and lung cancer. R. Rudd. 1997;52(3):306. Comment · Letter PubMed
Asbestos, Simian virus 40 and malignant mesothelioma. S.C. Stenton. 1997;52 Suppl 3(Suppl 3):S52-7. Review PubMed · Publisher · Free full text

Summary

This review discussed whether Simian virus 40 (SV40) might contribute, alongside asbestos, to malignant mesothelioma. It was prompted by an introductory article by Pepper and colleagues, in which SV40 primers amplified DNA of approximately the correct length in four of nine British mesotheliomas. The author noted that about 1000 cases were reported each year in Britain, with a predicted peak of up to 3000 per year around 2020, reflecting past amphibole asbestos use. Published studies were summarised. SV40-like DNA had been reported in 20 of 31 childhood brain tumours and in 29 of 48, and 8 of 11, mesotheliomas. Another group found none in 50 mesotheliomas. The author discussed possible technical explanations for these discrepancies, including laboratory contamination. Polio vaccines made in rhesus monkey kidney cells before 1961 were described as contaminated, with up to 30% thought to contain live SV40. Intrapleural SV40 produced mesotheliomas in all 12 injected hamsters in one study. SV40 large T antigen binds and inactivates tumour suppressor proteins, including p53 and the retinoblastoma protein. Asbestos fibres might help viral DNA enter cells. The author concluded that the reports required confirmation but raised the possibility that SV40 is an important cofactor. If about 5% of the general population and 60% of patients with mesothelioma carried the virus, this would suggest an approximately 30-fold increased risk. Cohort studies of vaccinated populations had limited power to detect such an effect.

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British Thoracic Society study of cryptogenic fibrosing alveolitis: current presentation and initial management. Fibrosing Alveolitis Subcommittee of the Research Committee of the British Thoracic Society. I.D. Johnston, R.J. Prescott, J.C. Chalmers, et al. 1997;52(1):38-44. PubMed · Publisher · Free full text

Abstract

Background: Mortality due to cryptogenic fibrosing alveolitis (CFA) is increasing, particularly in the elderly. Optimum management remains uncertain and previous studies of the disease have largely been from specialist centres. A national study was carried out of the presentation and initial management of CFA in the UK.

Methods: All respiratory physicians in England, Scotland and Wales were invited to enter patients with newly diagnosed CFA over a two year period. CFA was diagnosed on histological grounds or according to clinical criteria which included the absence of a defined connective tissue disorder or pneumoconiosis. Participating physicians (n = 150) completed a questionnaire at patient entry and at all subsequent follow up visits and death.

Results: A total of 588 patients (373 men, 63%) were studied of whom 441 (75%) were referrals from primary care. Their mean (SD) age was 67.4 (10.0) years and median duration of symptoms at presentation was 9.0 months. Clubbing was more common in men (203/373; 54%) than in women (86/ 215; 40%); 209 patients (36%) were graded as severely breathless at presentation. A history of dust exposure (organic or inorganic) was present in 274 patients (47%) of whom 87 had had some exposure to asbestos. Subjects exposed to dust were more likely to have smoked and had slightly higher mean lung volumes, but were otherwise indistinguishable from those not exposed in terms of clinical presentation, management, and outcome. Transbronchial biopsy specimens were taken in 164 patients (28%) and open lung biopsy specimens in 73 (12%), but 60% had no histological diagnostic procedure. Biopsy procedures were more likely to be performed in younger patients, those with better lung function, and those with a history of asbestos exposure. At presentation a decision not to initiate specific treatment was made in 284 cases (48%). The decision to initiate treatment was made predominantly on symptomatic grounds. Two years after the close of entry to the study 266 patients (45%) had died.

Conclusions: CFA is predominantly a disease of elderly patients and has a poor prognosis. Physicians generally considered CFA to be a clinical diagnosis and did not initiate treatment in up to half of patients at presentation.
Malignant mesothelioma in south east England: clinicopathological experience of 272 cases. D.H. Yates, B. Corrin, P.N. Stidolph, et al. 1997;52(6):507-12. PubMed · Publisher · Free full text

Abstract

Background: Malignant mesothelioma is a rare pleural tumour associated with asbestos exposure. The proportion of malignant mesothelioma unrelated to asbestos exposure, and any differentiating features between exposed and unexposed cases, are not well described. This study describes occupational, clinical, and pathological features in a large cohort of cases of malignant mesothelioma from south east England.

Methods: All 272 cases from this region were studied, either in life or after death when necropsy examination suggested malignant mesothelioma. Detailed information was gathered regarding the occupational history, clinical course, and mode of death. Necropsies were performed in 98% of cases. Lung tissue was examined histologically to confirm the diagnosis, subtype of tumour, presence or absence of asbestosis and asbestos bodies.

Results: Exposure to asbestos was documented in 87% of cases, while in the remainder, no asbestos exposure was found nor were asbestos bodies seen; 94.5% were pleural, 5.1% peritoneal, and 0.4% pericardial. Right sided tumours were more common than left sided tumours (ratio 1.6:1). Patients usually presented with breathlessness and chest pain, but 33% presented with pleural effusion in the absence of chest pain. The mean (SD) time from first exposure to asbestos to symptoms was 40 (12) years with a median (interquartile range (IQR) survival of 14 (12.5) months. The median (IQR) survival time in sarcomatous, epithelial, and mixed cell type malignant mesothelioma was 9.4 (10) months, 12.5 (18) months, and 11 (14) months, respectively, and was significantly greater in cases detected by chance. Clinical features were similar in asbestos related and non-asbestos related malignant mesothelioma.

Conclusions: In south east England most cases of malignant mesothelioma are associated with asbestos exposure. Clinical features do not differentiate between asbestos related and non-asbestos related disease.
Pericardial effusion associated with asbestos exposure. S. Trogrlic, P.A. Gevenois, M. Schroeven, et al. 1997;52(12):1097-8. Case report PubMed · Publisher · Free full text

Abstract

The case history is presented of a 60 year old man who developed a pericardial effusion. Chest radiography showed pleural thickening and calcification. Pericardiotomy was performed and revealed nonspecific inflammatory lesions. Occupational exposure to asbestos and exclusion of other causes led to the diagnosis of benign asbestos pericardial effusion.
The aetiology of mesothelioma: are risk factors other than asbestos exposure important?. R. Hubbard. 1997;52(6):496-7. Editorial PubMed · Publisher · Free full text

Summary

This editorial asked whether risk factors other than asbestos exposure are important in causing mesothelioma. The author noted that mesothelioma caused over 1000 deaths a year in England and Wales and cited predictions of about 3000 deaths a year by 2020. He commented on a study in the same issue by Yates et al, which reviewed 272 cases diagnosed in south east England, of whom 30 (11%) had no evidence of asbestos exposure. He considered it likely that a few patients develop the disease without asbestos exposure, although under-reporting of exposure and over-diagnosis may explain some cases. He described unrecognised exposure in occupations such as carpentry, electrical and construction work as an important public health issue. As evidence of spontaneous disease, he cited childhood cases: in one survey of 80 children, only two had a history of asbestos exposure. He also cited pleural tumours reported before the industrial use of asbestos. Other possible causes he discussed were erionite fibres in Cappadocia, Turkey, and, from anecdotal reports, sugar cane, ionising radiation and pleural scarring. He reviewed possible co-factors, including genetic susceptibility, smoking (no significant association in a controlled study) and Simian virus 40 (SV40). He concluded that most cases may be explained by asbestos exposure, but that spontaneous disease does occur and that SV40 as a possible co-carcinogen requires further investigation.

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Analysis and interpretation of inorganic mineral particles in "lung" tissues. A.R. Gibbs, F.D. Pooley. 1996;51(3):327-34. Review PubMed · Publisher · Free full text

Abstract

Mineral analysis of tissue specimens has provided very useful information in pathological conditions associated with occupational exposures to mineral particles, particularly when combined with epidemiological information. Most of the data have been related to exposures to fibrous particles such as asbestos. More investigations of this nature are required in diseases associated with exposure to non-fibrous particles. In the future it is likely that these types of investigation will be extended into the effects of pollutants.
Asbestos exposure, asbestosis, and asbestos-attributable lung cancer. R.N. Jones, J.M. Hughes, H. Weill. 1996;51 Suppl 2(Suppl 2):S9-15. Review PubMed · Publisher · Free full text

Summary

This review examined whether lung cancers attributable to asbestos are always associated with asbestosis (asbestos-induced lung fibrosis). The authors described this as a heated controversy with implications for regulation, workers' compensation and litigation. The review was written as a commentary on an introductory article, a case-control study by Wilkinson and colleagues (Lancet 1995), which reported an association between asbestos exposure and lung cancer in patients without radiographic small opacities. The authors traced the history of the evidence, from early case reports and Merewether's postmortem series to cohort studies of insulation and asbestos cement workers. They noted that Kipen et al found histological lung fibrosis in all 138 insulation workers with lung cancer who had acceptable tissue and radiographs. They also noted that Hughes and Weill found no excess lung cancer among asbestos cement workers without radiographic evidence of fibrosis. They criticised the Wilkinson study's exposure classification, its masking of radiographs and its dose-response findings, and judged that it did not provide convincing support for an asbestos-attributable risk in the absence of small opacities. They also reviewed evidence on lung fibrosis from other causes, registry studies, fibre burden studies, animal experiments, tumour site and cell type, and pleural plaques. They concluded that the issue was not settled, but that the weight of evidence strongly supported asbestosis as a necessary precursor. They stated that it was reasonable for judgements of attributability to rest on the presence of asbestosis diagnosed by radiography or histopathology.

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Lymphangitis carcinomatosa complicating primary malignant peritoneal mesothelioma. P.S. Craft, M.S. Reading, S. Jain, et al. 1996;51(5):552-3. Case report PubMed · Publisher · Free full text

Abstract

A patient with malignant peritoneal mesothelioma and a diffuse pulmonary infiltrate is described. Computed tomographic scanning suggested lymphangitis carcinomatosa. This was confirmed on transbronchial biopsy to be due to metastatic mesothelioma.
New developments in asbestos-related pleural disease. R.M. Rudd. 1996;51(2):210-6. Review PubMed · Publisher · Free full text

Summary

This review, part of a Thorax series on occupational lung disease, summarised evidence on benign pleural disease caused by asbestos. On pleural plaques, the author discussed how fibres may reach the parietal pleura. He cited an electron microscopy study that found asbestos fibres, almost all short chrysotile, in the parietal pleura in 16 of 29 cases and in lung tissue in 27 of 29. Plaques were described as rarely causing symptoms but as having prognostic significance: among 155 dockyard workers re-examined 10 years after pleural changes were found, 10.3% had radiographic opacities suggestive of asbestosis. A cited review found no convincing evidence that plaques predict lung cancer, and the author considered lung cancer risk likely to depend on asbestos dose rather than on plaques. Benign asbestos pleurisy with effusion was described as often bloodstained and as often followed by diffuse pleural thickening. For diffuse pleural thickening, the review covered lung fibre burdens, crackle patterns, chest radiograph and high resolution CT appearances including folded lung, a restrictive lung function pattern with reduced gas transfer, and biopsy. It noted that decortication seldom produced worthwhile improvement. The review also discussed CT-pathology studies of lung changes accompanying pleural disease, asbestos-related pericardial disease, and whether man-made mineral fibres cause similar changes.

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Simian virus 40 large T antigen (SV40LTAg) primer specific DNA amplification in human pleural mesothelioma tissue. C. Pepper, B. Jasani, H. Navabi, et al. 1996;51(11):1074-6. PubMed · Publisher · Free full text

Abstract

Background: DNA sequences and immunoreactivity associated with Simian virus 40 transforming factors, large T and small t antigens (SV40LTAg), suggestive of an aetiopathogenetic link have been identified in fresh frozen tissue of a high proportion of recent cases of pleural mesotheliomas from the United States, Italy and Germany. SV40 is not normally infective in man though it can transform human cells in tissue culture. A large cohort of people in the western world was accidentally parenterally inoculated with live SV40 through contaminated polio vaccines given between 1959 and 1961, and this might be a factor in the current continuing rise in the incidence of mesothelioma in the United States, Britain and Europe. The present study investigated the presence of SV40LTAg DNA in recently diagnosed cases of mesothelioma in Britain and the feasibility of detecting the SV40 DNA in archival tissue for retrospective analysis of cases in the peri-vaccination period.

Methods: DNA was extracted from fresh frozen and/or rehydrated formalin fixed, paraffin embedded tissue sections from nine recently diagnosed cases of mesothelioma, nine cases of pulmonary adenocarcinoma, and three reactive pleurae, and amplified by the polymerase chain reaction (PCR) using the primer pairs used previously on fresh frozen tissues-namely, the SV primer set directed at the LTAg gene sequence unique to SV40 and the PYV primer set directed at a sequence shared by SV40 and papovavirus strains BK and JC, respectively.

Results: PCR positivity with the SV primer set was restricted to four of the nine cases of mesothelioma. In contrast, six of the nine mesotheliomas, two of the nine adenocarcinomas, and one of the three reactive pleurae showed positivity with the PYV primers. The fresh frozen and corresponding formalin fixed, paraffin embedded tissue results concorded well with each other.

Conclusions: Our data provide evidence for the association of SV40LTAg primer specific DNA with human pulmonary mesothelioma in the British population.
Two dimensional protein patterns of bronchoalveolar lavage fluid from non-smokers, smokers, and subjects exposed to asbestos. M. Lindahl, T. Ekström, J. Sörensen, et al. 1996;51(10):1028-35. PubMed · Publisher · Free full text

Abstract

Background: Bronchoalveolar lavage (BAL) fluid contains a large number of proteins which comprise a potential resource for studying respiratory effects due to occupational and environmental exposures. A study was undertaken to compare protein patterns of BAL fluid from non-smokers, smokers, and subjects exposed to asbestos.

Methods: BAL fluid samples were analysed with two dimensional gel electrophoresis (2-DE). The separated proteins were detected, quantified, and pattern-matched between different individuals with a computerised imaging system designed for evaluations of 2-DE patterns.

Results: About 200 different protein spots were detected in each sample of BAL fluid. As is the case with blood plasma, the BAL fluid samples contained large amounts of albumin, transferrin, and immunoglobulins. Higher levels of basic proteins were found in smokers than in non-smokers, while subjects exposed to asbestos had increased amounts of several high molecular weight proteins as well as basic proteins. Lower levels of albumin and higher levels of immunoglobulins were found in smokers than in non-smokers, while higher levels of transferrin were found in asbestos exposed subjects than in unexposed subjects. Moreover, in the group exposed to asbestos differences were found between patients with pleuritis and patients with pleural plaque, and one protein spot was found only in two patients with progressive pleural disease.

Conclusion: These results suggest that both smokers and asbestos exposed subjects have significant changes in their airway protein expression compared with non-smokers and unexposed subjects. It is inferred that analysis of protein patterns in the BAL fluid with 2-DE may be used to detect and characterise, at a molecular level, respiratory effects due to occupational and environmental exposures.
Malignant mesothelioma: new insights into tumour biology and immunology as a basis for new treatment approaches. J.W. Upham, M.J. Garlepp, A.W. Musk, et al. 1995;50(8):887-93. Review PubMed · Publisher · Free full text

Summary

This review, by authors at the University of Western Australia, examined recent laboratory and clinical findings on the biology and immunology of malignant mesothelioma and how they might inform new treatments. The authors noted that mesothelioma incidence had risen as a result of asbestos mining and industrial use, and was predicted to keep rising for another 20 years. They reported that conventional surgery, radiotherapy and chemotherapy had proved disappointing. One review of single agent chemotherapy had found an average response rate of 13% in 21 trials covering 552 patients. They summarised evidence on growth factors such as PDGF and TGF-beta and on tumour suppressor genes, including homozygous p16 deletions in 85% of a series of cell lines and in 22% of primary tumours. They also described the immune response to the tumour and how mesothelioma cells may evade it. They outlined gene transfer experiments in mice, including B7-1 transfection, and clinical studies of cytokines. Systemic interferon alpha 2a produced significant tumour reductions in 16% of patients, and intrapleural interferon gamma produced responses in about one third. Photodynamic therapy, immunoconjugates, chemohyperthermia, gene therapy, vaccines and preventive agents such as vitamin A derivatives in asbestos-exposed populations were also discussed. The authors concluded that recent research gave grounds for cautious optimism that these new approaches would be successfully applied to treatment.

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In plain English

This 1995 article was a review, not a new study. The authors reviewed laboratory research (human and rodent mesothelioma cell lines and animal models) and early clinical studies on malignant mesothelioma, as a basis for new treatments. They described conventional surgery, radiotherapy and chemotherapy as disappointing. An earlier review they cited found an average response rate of 13% across 21 single-drug chemotherapy trials covering 552 patients. They summarised reports on growth factors, tumour suppressor genes such as p16, and ways the tumour may evade the immune system. In clinical studies they cited, tumour bulk fell significantly in 16% of patients in one interferon alpha trial. About one third of patients responded to interferon gamma given into the pleural cavity. They also described their own unpublished mouse experiments and early trials delivering cytokines directly into the tumour. Preliminary results from giving interferon alpha 2b or GM-CSF continuously into the tumour suggested this was feasible and caused fewer side effects than systemic therapy. It was too early to tell whether tumours shrank. The authors expressed cautious optimism about new approaches and noted significant obstacles, including cost.

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Pleural mesothelioma with non-Hodgkin's lymphoma. P. Hughes, C.R. McGavin. 1995;50(8):915. Case report · Letter PubMed · Publisher · Free full text

Summary

This letter to the editor responded to a case reported by Tondini and colleagues (Thorax, December 1994;49:1269-70) of non-Hodgkin's lymphoma in an asbestos worker with mesothelioma. The authors noted that lymphoproliferative disorders were not recognised as prescribed asbestos-related diseases, although Tondini's case and others had attempted to make this relationship. The authors, from the Department of Respiratory Medicine at the Plymouth Chest Clinic, Freedom Fields Hospital, Plymouth, UK, described a further case. A 60-year-old man developed histologically proven mesothelioma after heavy exposure to asbestos in the Devonport dockyard. He presented with a pleural effusion and died 15 months later. At necropsy an ulcerating mass was found in the stomach, and biopsies of the lesion showed a lymphocytic lymphoma. Contrary to the view of Tondini and colleagues, the authors stated that the association between gastrointestinal cancer and asbestos had not been conclusively proven. They cited a re-assessment of the evidence on that question. They added that an increased incidence of exposure to asbestos had been noted in a study of gastric lymphoma. The authors offered their case as an addition to those referred to by Tondini and colleagues. They agreed that further study of the relationship between lymphoma and asbestos should be conducted.

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Pleurectomy for persistent pain in benign asbestos-related pleural disease. D.I. Fielding, J.L. McKeon, W.A. Oliver, et al. 1995;50(2):181-3. PubMed · Publisher · Free full text

Abstract

Background: Persistent severe pain is a rare complication of benign asbestos-related pleural disease.

Methods: Four patients are described in whom pain persisted for more than one year (range 18 months to five years) which was incompletely relieved by opioid medication and nerve blocking procedures. All underwent pleurectomy in an attempt to relieve it.

Results: At operation the pleura was considerably thickened in all cases. Two of the four patients had successful relief of pain. The other two had a neuralgic component to their pain before surgery which persisted afterwards. One of these patients underwent successful cervical cordotomy.

Conclusions: Pleurectomy may provide relief in patients with constant pleuritic pain due to benign asbestos-related pleural thickening. It seems, however, that patients in whom the pain has a neuralgic component are unlikely to benefit.
Pleural mesothelioma associated with non-Hodgkin's lymphoma. M. Tondini, G. Rocco, M. Travaglini, et al. 1994;49(12):1269-70. Case report · Review PubMed · Publisher · Free full text

Abstract

Occupational exposure to asbestos has been associated with an increased incidence of lung and gastric cancers, mesotheliomas, and myelolymphoid malignancies. A new observation of a patient with indirect exposure to asbestos who developed mesothelioma and plasmacytoid lymphocytic non-Hodgkin's lymphoma is described. This report and the previously described stimulation of B lymphocytes by asbestos suggests that the association of mesothelioma with lymphoid and plasma cell malignancies is not merely a coincidence.
Diagnosis of asbestosis by a time expanded wave form analysis, auscultation and high resolution computed tomography: a comparative study. N. al Jarad, B. Strickland, G. Bothamley, et al. 1993;48(4):347-53. PubMed · Publisher · Free full text

Abstract

Background: Crackles are a prominent clinical feature of asbestosis and may be an early sign of the condition. Auscultation, however, is subjective and interexaminer disagreement is a problem. Computerised lung sound analysis can visualise, store, and analyse lung sounds and disagreement on the presence of crackles is minimal. High resolution computed tomography (HRCT) is superior to chest radiography in detecting early signs of asbestosis. The aim of this study was to compare clinical auscultation, time expanded wave form analysis (TEW), chest radiography, and HRCT in detecting signs of asbestosis in asbestos workers.

Methods: Fifty three asbestos workers (51 men and two women) were investigated. Chest radiography and HRCT were assessed by two independent readers for detection of interstitial opacities. HRCT was performed in the supine position with additional sections at the bases in the prone position. Auscultation for persistent fine inspiratory crackles was performed by two independent examiners unacquainted with the diagnosis. TEW analysis was obtained from a 33 second recording of lung sounds over the lung bases. TEW and auscultation were performed in a control group of 13 subjects who had a normal chest radiograph. There were 10 current smokers and three previous smokers. In asbestos workers the extent of pulmonary opacities on the chest radiograph was scored according to the International Labour Office (ILO) scale. Patients were divided into two groups: 21 patients in whom the chest radiograph was > 1/0 (group 1) and 32 patients in whom the chest radiograph was scored < or = 1/0 (group 2) on the ILO scale.

Results: In patients with an ILO score of < or = 1/0 repetitive mid to late inspiratory crackles were detected by auscultation in seven (22%) patients and by TEW in 14 (44%). HRCT detected definite interstitial opacities in 11 (34%) and gravity dependent subpleural lines in two (6%) patients. All but two patients with evidence of interstitial disease or gravity dependent subpleural lines on HRCT had crackles detected by TEW. In patients with an ILO score of > 1/0 auscultation and TEW revealed mid to late inspiratory crackles in all patients, whereas HRCT revealed gravity dependent subpleural lines in one patient and signs of definite interstitial fibrosis in the rest. In normal subjects crackles different from those detected in asbestosis were detected by TEW in three subjects but only in one subject by auscultation. These were early, fine inspiratory crackles.

Conclusion: Mid to late inspiratory crackles in asbestos workers are detected by TEW more frequently than by auscultation. Signs of early asbestosis not apparent on the plain radiograph are detected by TEW and HRCT with similar frequency. off
Liposarcomatous differentiation in diffuse pleural mesothelioma. J. Krishna, M.T. Haqqani. 1993;48(4):409-10. Case report PubMed · Publisher · Free full text

Abstract

A case history is presented of a woman who died eight hours after hospital admission with severe breathlessness. At necropsy the right lung was encased in a thickened pleura with a large tumour. Histological examination of the tumour showed pleural mesothelioma with liposarcomatous differentiation. The lungs showed changes of asbestosis and the asbestos fibre count was significantly raised. Liposarcomatous differentiation in pleural mesothelioma has not been reported previously.
Malignant mesothelioma in women. A. Dawson, A.R. Gibbs, F.D. Pooley, et al. 1993;48(3):269-74. PubMed · Publisher · Free full text

Abstract

Background: Malignant mesothelioma reportedly shows different epidemiology and pathology in females, and a proportion are believed to arise spontaneously.

Methods: One hundred and seventy seven cases of malignant mesothelioma in females were reviewed, examined by histochemistry and immunohistochemistry, assessed for asbestosis and lung fibre burden by transmission electron microscopy with energy dispersive x ray analysis, and compared with 31 female controls.

Results: Two of one hundred and three cases tested for carcinoembryonic antigen were positive and were excluded from further analysis. Tumour cases showed increased amphibole burdens; in those in whom exposure information was known, 74 (80%) of 93 patients had a history of exposure to asbestos. Seventy two (47%) of 152 patients had lung fibrosis. Tumour site and histological type were little different from those reported in adult males. Mixed type histological pattern, lung fibrosis, and peritoneal site were associated with heavier lung asbestos burdens, but not exclusively. Thirty five (30%) of 117 patients had amphibole burdens of less than 2 x 10(6) fibres/g; the sites affected and the histological pattern of tumours in this group were similar to those in cases with amphibole fibre counts of > or = 2 x 10(6)/g lung. A higher lung amphibole burden than the mean burden in control females was found in 115 (98%) of 117 patients tested.

Conclusions: The pathology of malignant mesothelioma appears to be similar in women and in men, and in cases associated and unassociated with asbestos.
New perspectives on basic mechanisms in lung disease. 5. Respirable industrial fibres: mechanisms of pathogenicity. K. Donaldson, R.C. Brown, G.M. Brown. 1993;48(4):390-5. Review PubMed · Publisher · Free full text

Summary

This review, part of a British Association for Lung Research series, addressed the scientific ideas behind research into how respirable industrial fibres cause disease. The fibres covered were asbestos and natural and man-made non-asbestos fibres. The authors noted that asbestos inhalation is associated with asbestosis, lung carcinoma, mesothelioma and small airways disease. They also noted that some non-asbestos fibres caused asbestos-like effects in biological assays, which raised the question of whether all fibres share asbestos's pathogenic potential. They summarised evidence on fibre deposition, length, surface chemistry and durability. In rat studies, a long-fibre amosite sample produced lung tumours in 32.5% of animals after inhalation and mesotheliomas in 88% after intraperitoneal instillation, while a short-fibre sample produced none. Other evidence reviewed included the following: long fibres were cleared less effectively; surface chemistry (erionite, protein coating, iron) may influence activity; and epidemiological studies suggested chrysotile is much less harmful in man than other asbestos forms. The authors also reviewed fibre effects on epithelial cells, macrophages, inflammation and mesothelial cells, and combined exposures with smoking, ozone and other dusts. They noted that standard non-asbestos fibre samples had been lacking and that the UICC asbestos samples contained mostly short fibres. They concluded that the idea that any long, thin, durable fibre may be pathogenic dominates the field, although there is no consensus on definitions of these terms. They suggested that understanding which fibre characteristics control toxicity may allow industry to design safer fibres.

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Abnormal lung function associated with asbestos disease of the pleura, the lung, and both: a comparative analysis. K.H. Kilburn, R.H. Warshaw. 1991;46(1):33-8. PubMed · Publisher · Free full text

Abstract

The impairment of lung function associated with different types of asbestos related disease was examined in 1298 men. The 310 men with circumscribed pleural lesions (plaques) or diffuse pleural thickening without asbestosis were compared with 596 men with asbestosis only and with 322 men with pleural abnormalities and asbestosis, as classified from chest radiographs by ILO pneumoconiosis criteria. Spirometric indices and total lung capacity (TLC; determined by planimetry) were measured and expressed as percentages of predicted values. Non-smoking men with pleural disease only had reduced values of mid and terminal expiratory flows (80.6 and 69.9% predicted) and a reduced FEV1 (89% predicted) with a forced vital capacity (FVC) of 94% predicted. TLC was 104% predicted. Thus they had airways obstruction with-out restriction. Non-smoking men with pulmonary asbestosis (ILO profusion of opacities mostly 1/0 and 1/1) had pulmonary function similar to that of men with pleural disease. FEV1 and FVC and flow rates at other lung volumes were lower in smokers with asbestosis (after adjustment for duration of smoking) than in the non-smokers with asbestosis. Airflow limitation was worse in the men with both pleural abnormalities and pulmonary asbestosis with lower values for mid expiratory flow, FEV1 and FVC (but not TLC) than those with either abnormality alone, in both non-smokers and current smokers. Men with diffuse pleural thickening that included the costophrenic angles had more airways obstruction and air trapping and lower FVC values than those with circumscribed pleural disease.
Asbestos induced pericardial effusion and constrictive pericarditis. D. Davies, M.I. Andrews, J.S. Jones. 1991;46(6):429-32. Case report PubMed · Publisher · Free full text

Abstract

The number of disorders attributable to asbestos exposure has increased gradually over the years. The latest to be recorded is pericardial effusion and constrictive pericarditis, and three cases are reported here. A man with bilateral pleural thickening and plaques developed acute pericarditis and an effusion and was treated by pericardiectomy. Two men died from constrictive pericarditis associated with bilateral pleural effusions and diffusion pleural thickening. The pericardium showed nonspecific fibrous thickening. All had been occupationally exposed to asbestos. In the fatal cases the lungs contained amphibole fibres, in keeping with a modest degree of occupational exposure. Asbestos produces progressive fibrosis of the pericardium that is similar to diffuse pleural thickening and may be fatal. Both conditions may develop after relatively short or light exposure.
Pneumothorax and malignant mesothelioma in patients over the age of 40. J.D. Sheard, W. Taylor, A. Soorae, et al. 1991;46(8):584-5. PubMed · Publisher · Free full text

Abstract

Five patients over the age of 40 with malignant mesothelioma of the pleura presented with a spontaneous pneumothorax in the course of five years. The diagnosis of malignant mesothelioma was not suspected at surgery but was made by histological examination of the pleurectomy specimens. During this time 91 pleurectomies for recurrent pneumothorax were performed, 45 in patients over the age of 40; malignant mesothelioma therefore accounted for 11% of spontaneous pneumothorax requiring pleurectomy in this age group. The association of spontaneous pneumothorax and malignant mesothelioma is not emphasised in current publications. These five cases highlight the need for all pleurectomy specimens in cases of spontaneous pneumothorax to be sent for histological examination and for a full occupational history to be taken, especially in older patients.
Prevalence of obstructive lung disease in a general population: relation to occupational title and exposure to some airborne agents. P.S. Bakke, V. Baste, R. Hanoa, et al. 1991;46(12):863-70. PubMed · Publisher · Free full text

Abstract

Background: The importance of occupational exposure to airborne agents in the development of obstructive disease is uncertain. Studying the relation in a community population has the benefit of reducing the healthy worker effect seen in studies of working populations.

Methods: The prevalence of obstructive lung disease was examined in a Norwegian general population aged 18-73 in a two phased cross sectional survey. In the second phase a stratified sample (n = 1512) of those responding in the first phase was invited for clinical and spirometric examination (attendance rate 84%). Attenders were asked to state all jobs lasting greater than 6 months since leaving school and to say whether they had been exposed to any of seven specific agents and work processes potentially harmful to the lungs.

Results: The prevalence of asthma and chronic obstructive lung disease was 2.4% and 5.4%, respectively; spirometric airflow limitation (FEV1/FVC less than 0.7 and FEV1 less than 80% of predicted values) was observed in 4.5% of the population. All jobs were categorised into three groups according to the degree of potential airborne exposure. Having a job with a high degree of airborne exposure increased the sex, age, and smoking adjusted odds ratio for obstructive lung disease (asthma and chronic obstructive lung disease) by 3.6 (95% confidence interval 1.3 to 9.9) compared with having a job without airborne exposure; the association with spirometric airflow limitation was 1.4 (0.3 to 5.2). Occupational exposures to quartz, metal gases, aluminium production and processing, and welding were significantly associated with obstructive lung disease after adjusting for sex, age, and smoking habit, the adjusted odds ratios varying between 2.3 and 2.7. Occupational exposure to quartz and asbestos was significantly related to spirometric airflow limitation in people older than 50.

Conclusion: Occupational title and exposure to specific agents and work processes may be independent markers of obstructive lung disease in the general population.
Diffuse meningeal thickening associated with pleural mesothelioma. M. Huncharek, J. Muscat. 1990;45(7):571. Case report · Comment · Letter PubMed · Publisher · Free full text
Pleuroperitoneal shunt for recurrent malignant pleural effusions. V. Tsang, H.C. Fernando, P. Goldstraw. 1990;45(5):369-72. PubMed · Publisher · Free full text

Abstract

The therapeutic options available for the management of malignant pleural effusions associated with a restricting malignant cortex remain unsatisfactory. The efficacy of pleuroperitoneal shunts was evaluated in 16 patients with recurrent malignant effusions. There were no operative deaths; one patient died on the third postoperative day as a result of lymphangitis carcinomatosa. The median hospital stay was five (range 3-21) days. Palliation was obtained in all but one of the other 15 patients. There was no appreciable reaccumulation of pleural fluid as judged by radiography. Two patients developed occlusion of the shunt. In one case this was due to blood clots in the pleural catheter and necessitated insertion of a new shunt. The other shunt was removed because of obstructing infected fibrin debris, and a rib resection was performed. There were eight deaths related to the underlying malignancy after a mean interval of 7.3 (range 1.5-23) months. The other six patients are still alive, with a mean survival of 11.0 (range 5-20) months, and have achieved good symptomatic relief. The insertion of a pleuroperitoneal shunt can offer effective palliation for patients with recurrent malignant pleural effusions.
Role of asbestos and other fibres in the development of diffuse malignant mesothelioma. A.R. Gibbs. 1990;45(9):649-54. Review PubMed · Publisher · Free full text

1980s

Malignant pleural mesothelioma in western Glasgow 1980-6. G. Hulks, J.S. Thomas, E. Waclawski. 1989;44(6):496-500. PubMed · Publisher · Free full text

Abstract

This study reviews all histologically proved cases of malignant pleural mesothelioma seen in the western district of Glasgow during 1980-6. Sixty eight cases were identified (three female) with an age range at presentation of 48-85 (mean 68.9) years. Asbestos exposure was identified in 54 (80%) of the patients, most of whom had been shipyard workers. Pain and dyspnoea were the most common presenting symptoms. Pleural effusion was found in 57 (84%) of the patients, in a ratio of 2.6 right:left. The median survival was only 30 weeks from the time of presentation. Prognosis was significantly better for those presenting with dyspnoea than for those with pain (median survival 44 v 22 weeks). Postmortem examination was performed in 40 cases and metastatic disease found in more than three quarters. There was no significant difference between the incidence of the various tumour cell types or any relation between cell type and survival or the incidence of metastatic disease. A substantial increase in cases of malignant pleural mesothelioma has been found in an area of already high incidence. The use of rigorous histological criteria to determine histological cell type has shown that this previously valued variable is of no discriminatory value with regard to disease activity or survival.
Palliation of malignant ascites with a Tenckhoff catheter. D.A. Lomas, P.J. Wallis, R.A. Stockley. 1989;44(10):828. Case report PubMed · Publisher · Free full text

Abstract

To avoid multiple paracenteses, a Tenckhoff catheter was used successfully to drain the ascitic fluid in a patient with peritoneal mesothelioma.
Relation of airway responsiveness to duration of work in a dusty environment. P. Ernst, R.E. Dales, F. Nunes, et al. 1989;44(2):116-20. PubMed · Publisher · Free full text

Abstract

Health selection within a workforce has been found in several industries and appears to be more pronounced in dustier occupations. In this study of airway disease among workers exposed to asbestos and man made mineral fibres, 215 of 246 construction insulators 50 years old or less and currently working in the Montreal area were examined. Spirometry was completed successfully in 214 workers without known asbestosis and 207 underwent methacholine bronchoprovocation testing. Airway responsiveness was expressed as PC15, the concentration of methacholine causing a 15% fall in the forced expiratory volume in one second (FEV1). Exposure to asbestos and synthetic mineral fibre dust was estimated from the total hours of work in the trade since first employment. After the effect of age, height, and pack years of smoking had been taken into account, no relation was found between hours of work and any indices obtained from the forced expiratory manoeuvre (FEV1/FVC, MMF). After the effect of airway calibre (FEV1/FVC), age, and pack years of cigarette consumption had been taken into account, airway responsiveness decreased as the total hours of work in the trade increased. These findings suggest that workers with greater levels of airway responsiveness are more sensitive to exposure in a dusty workplace and in consequence are less likely to continue. In studies of workforces a survivor effect of this nature will tend to weaken the relation between lung function abnormality and occupational exposure.
Bony metastases in desmoplastic pleural mesothelioma. T. Machin, E.T. Mashiyama, J.A. Henderson, et al. 1988;43(2):155-6. Case report PubMed · Publisher · Free full text

Summary

The authors, from Long Beach, California, and Ottawa, Canada, described two patients with desmoplastic pleural mesothelioma, a mainly fibrous variant of diffuse malignant mesothelioma that can be hard to distinguish from fibrous pleurisy. In both, bone metastases were the first clinical evidence that the tumour had spread. A 78 year old man had a left pleural effusion and pleural thickening. Pleural biopsy specimens were interpreted as fibrous pleurisy. Ten months later lytic lesions appeared in the pelvic bones and spine, and an iliac crest biopsy showed fibrous tumour. He died two months later. There was no history of exposure to asbestos. A 70 year old man had breathlessness, chest tightness, cough and right sided chest pain, with a right pleural effusion and thickened pleura (0.4-0.8 cm). Pleural biopsy specimens were interpreted as chronic pleuritis. About five months later lytic areas were seen in both humeri, and bone scans showed increased activity in the humeri, femurs and both 8th ribs. A month after a right humerus biopsy he had a pathological fracture of the left humerus and died shortly after surgery. Neither patient had a necropsy. In retrospect, the authors found that necrosis, nuclear atypia and complex tissue patterns in the pleural biopsies had been clues to tumour. They concluded that the cases emphasised the potential for misdiagnosing diffuse pleural fibrous lesions.

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Bronchoalveolar lavage in talc induced lung disease. A.A. Redondo, D.B. Ettensohn, M. Khan, et al. 1988;43(12):1019-21. Case report PubMed · Publisher · Free full text

Abstract

A 65 year old woman with a history of occupational talc inhalation presented with hypoxaemia, cough, and dyspnoea with a normal chest radiograph. Bronchoalveolar lavage showed considerable lymphocytosis, with a predominance of T8+ T lymphocytes, and open lung biopsy showed peribronchiolar granulomas containing talc crystals. Corticosteroid treatment resulted in dramatic improvement. Bronchoalveolar lavage may aid in the diagnosis of talc related lung injury.
Desmoplastic mesothelioma. J.S. Thomas, R.A. Burnett. 1988;43(7):584. Letter PubMed · Publisher · Free full text
Kinetics of the bronchoalveolar leucocyte response in rats during exposure to equal airborne mass concentrations of quartz, chrysotile asbestos, or titanium dioxide. K. Donaldson, R.E. Bolton, A. Jones, et al. 1988;43(7):525-33. PubMed · Publisher · Free full text

Abstract

The kinetics of the bronchoalveolar response was assessed in rats exposed, at equal airborne mass concentration (10 mg/m3), to titanium dioxide--a non-pathogenic dust--and the two pathogenic mineral dusts quartz and chrysotile asbestos. Rats were killed at intervals over a 75 day exposure period and groups of rats exposed for 32 and 75 days after recovery for two months. Bronchoalveolar lavage was carried out and the lavage fluid characterised for cellular content, macrophage activation, and concentrations of free total protein, lactate dehydrogenase, and N-acetyl-beta-D-glucosaminidase. Inhalation exposure to the two pathogenic dusts resulted in an increased number of leucocytes, macrophage activation, and increased levels of free enzymes and total protein. The pattern and magnitude of the responses to quartz and chrysotile differed. Chrysotile caused less inflammation than quartz, and the main cellular response peaked around the middle of the period of dust exposure whereas the highest levels of enzymes occurred towards the end. The difference in timing suggests that macrophages were not available for lavage towards the end of the exposure, owing to their playing a part possibly in deposition of granulation tissue. Quartz caused a greater cellular and enzyme response than chrysotile, particularly towards the end of the dust exposure phase. There was a noticeable progression of inflammation in the quartz exposed groups left to recover for two months, but not in the chrysotile recovery groups.
Lung function 22-35 years after treatment of idiopathic spontaneous pneumothorax with talc poudrage or simple drainage. P. Lange, J. Mortensen, S. Groth. 1988;43(7):559-61. PubMed · Publisher · Free full text

Abstract

The long term effects on lung function of treatment of idiopathic spontaneous pneumothorax by talc poudrage or simple chest drainage were assessed in 114 patients. Subjects were studied 22-35 years after their first pneumothorax with measurement of static and dynamic lung volumes. Eighty patients had been treated with talc pleurodesis and 34 with simple pleural drainage. At the follow up examination 17 had died from what appear to be unrelated causes and two had emigrated. Of the remainder, 75 participated fully in the study, 14 completed a postal questionnaire, and six failed to respond. The group treated with talc poudrage showed a mild restrictive impairment of lung function with a mean total lung capacity (TLC) of 89% predicted. In subjects treated with simple drainage mean TLC was 96% predicted. One subject treated with talc poudrage had extensive pleural calcification and a substantial reduction in lung function (TLC 58% predicted) with some evidence of lung fibrosis. None of the subjects had developed a mesothelioma. We conclude that, although talc poudrage may cause a mild restrictive impairment of lung function and pleural thickening on the chest radiograph, the long term outlook is good.
Relationship of lung function to radiographic reading (ILO) in patients with asbestos related lung disease. J.E. Cotes, B. King. 1988;43(10):777-83. PubMed · Publisher · Free full text

Abstract

The 1980 International Labour Office (ILO) classification of posteroanterior chest radiographs was used to obtain the scores for profusion of small opacities and pleural abnormalities of 172 men with confirmed or suspected disease of the lungs due to asbestos. After allowance had been made for age, stature, and smoking habit the quantitative score for area of diffuse pleural thickening seen in profile on both lateral chest walls contributed to reductions in inspiratory capacity, expiratory reserve volume, and forced expiratory flow rates. Occlusion of one or both costophrenic angles in the presence of diffuse thickening was associated with further reduction in inspiratory capacity. Profusion of small opacities was associated with a reduction in transfer factor. Diffuse pleural thickening and occlusion of costophrenic angles were associated with relatively low values for the forced expiratory flow rates (MEF50FVC) and FEV1/FVC, whereas small opacities were associated with relatively high values. Thus overall increased, normal, or reduced values of MEF50FVC and FEV1/FVC might occur, depending on the distribution of the radiographic abnormalities. The findings contribute to the validation of the ILO pleural scores; those for diffuse pleural thickening and occlusion of costophrenic angles should be used jointly with the scores for profusion of parenchymal small opacities in interpreting the lung function of persons exposed to asbestos.
Asbestos induced diffuse pleural fibrosis: pathology and mineralogy. M. Stephens, A.R. Gibbs, F.D. Pooley, et al. 1987;42(8):583-8. PubMed · Publisher · Free full text

Abstract

Lungs from seven cases of diffuse pleural fibrosis with known asbestos exposure were studied to determine the gross and microscopic pathological features and relate these to the analysed mineral fibre content of the lung. All seven individuals had had substantial exposure, ranging from two to 25 years, and chronic chest problems and at necropsy all cases met the criteria for compensatable disease. Macroscopically, all had extensive visceral pleural fibrosis and extensive areas of adhesions, and four also had discrete parietal pleural plaques. The histological features were similar in all the cases--most strikingly the basket weave pattern of the thickened pleura and a dense subpleural parenchymal interstitial fibrosis with fine honeycombing, extending up to 1 cm into the underlying lung. The similar histological appearances raise the possibility that diffuse pleural fibrosis and pleural plaques have a similar pathogenesis. Amphibole asbestos (crocidolite and amosite) counts were high in six of the seven cases and chrysotile counts in four; four cases had high mullite counts, but the importance of this is not known. It is concluded that diffuse pleural fibrosis is a specific asbestos associated entity, of uncertain pathogenesis, with mineral fibre counts falling between those found with plaques and those in minimal asbestosis.
Asbestos pleural effusion: a clinical entity. G. Mårtensson, S. Hagberg, K. Pettersson, et al. 1987;42(9):646-51. PubMed · Publisher · Free full text

Abstract

In a case-control study asbestos exposure in 64 consecutive men with idiopathic pleural effusion and 129 randomly sampled age matched male controls was compared. Furthermore, seven women and 64 men with idiopathic pleural effusion were studied, including a three year re-examination, in an attempt to identify characteristics that might distinguish asbestos exposed from non-exposed patients. Asbestos exposure was significantly (p less than 0.01) more frequent in men with idiopathic effusions than in controls. The idiopathic effusions seen in asbestos exposed patients were compatible with the diagnosis "asbestos pleural effusion." Two features were characteristic of patients with asbestos pleural effusion: a chest radiograph at the initial examination showing converging pleural linear structures or rounded atelectasis or a history of recurrent pleural effusion, or both.
Mesothelioma in Cyprus: the role of tremolite. K. McConnochie, L. Simonato, P. Mavrides, et al. 1987;42(5):342-7. Case report PubMed · Publisher · Free full text

Abstract

There is a chrysotile mine in the central mountains of Cyprus but no other appreciable source of industrial asbestos. Hence the island was thought to offer ideal conditions to seek pure chrysotile induced mesothelioma. The first reported case was a village woman whose lung tissue contained amphibole asbestos fibres, which were later identified as tremolite. This began a search for the origin of her exposure to asbestos. Our studies have shown that tremolite is widespread, being found, along with chrysotile, in domestic and environmental dust samples. Other cases of mesothelioma have been diagnosed, and the pattern of their distribution suggests that the mine is not the major source of disease. Exposure to tremolite is equally, if not more, important.
Metastases in diffuse pleural mesothelioma: influence of histological type. M. Huncharek, J. Muscat. 1987;42(11):897-8. PubMed · Publisher · Free full text

Summary

This short report examined how often diffuse pleural mesothelioma spreads to distant sites, and whether this depends on histological type. Earlier reports had stressed that metastases were infrequent, while some suggested that blood-borne spread was characteristic of the sarcomatous type. The authors reviewed 42 cases (40 men, two women) proved histologically after complete necropsy. A pathologist of the Canadian Tumor Reference Center confirmed each diagnosis. Medical records and necropsy and pathology reports were reviewed. Tumours were classed as epithelial, sarcomatous or mixed, and a chi-square analysis tested the relation between cell type and distant metastases. Median age was 62 years (range 45-80). Distant metastases were found at necropsy in 32 of the 42 cases (76%). The commonest sites were the contralateral lung (16 cases), kidney (11), liver (9) and adrenals (8). Regional lymph node metastases were found in 19 cases (45%). Thirty-eight subjects (90%) had documented occupational asbestos exposure (mean 20.9 years). One woman had domestic exposure, and histories were unavailable for three men. Metastases occurred in 75% of epithelial, 70% of sarcomatous and 83% of mixed tumours. There was no statistically significant association between histological type and metastases, or between histological type and age at diagnosis. The authors concluded that distant metastases are a common feature of diffuse pleural mesothelioma and that all three cell types are associated with metastatic spread.

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Metastatic renal cell carcinoma mimicking pleural mesothelioma. D.R. Taylor, W. Page, D. Hughes, et al. 1987;42(11):901-2. Case report PubMed · Publisher · Free full text

Summary

The authors, from the Departments of Medicine and Pathology at The Queen's University of Belfast, reported a case of renal cell carcinoma that spread to the pleura and mimicked pleural mesothelioma. A 67 year old man had a six week history of dry cough, increasing breathlessness and left sided pleuritic chest pain. He had smoked 40 pack years and had been exposed to asbestos 25 years earlier while working as a boiler engineer. He had a left pleural effusion and a 6 cm mass in the left upper abdomen. Cytology of the pleural fluid showed no malignant cells. Computed tomography suggested mesothelioma or metastatic disease, with no pleural plaques. Abdominal scans showed a solid mass typical of renal cell carcinoma. Because of the asbestos history and the radiological appearances, mesothelioma was the clinical diagnosis, and the abdominal mass was thought to be a benign cyst. He died in respiratory failure after about four months. At necropsy, tumour filled the left pleural space and had grown along the track of a chest drain. The tumour looked like mesothelioma to the naked eye. However, histology and immunocytochemistry showed renal cell carcinoma and excluded mesothelioma. The right lung showed asbestos fibres and early asbestosis. The authors stated that whether asbestos was a cause in this case could not be established. They said the case is a reminder that asbestos is a possible cause of some non-respiratory tract tumours.

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Mortality in cases of asbestosis diagnosed by a pneumoconiosis medical panel. I.I. Coutts, J.C. Gilson, I.H. Kerr, et al. 1987;42(2):111-6. PubMed · Publisher · Free full text

Abstract

One hundred and fifty five male cases of asbestosis certified by the London Pneumoconiosis Medical Panel during 1968-74 were followed up during 1978-9, 4-11 (mean 7.5) years after certification. Fifty nine patients had died, 23 (39%) from lung cancer, 6 (10%) from mesothelioma, and 11 (19%) from other respiratory causes. The number of observed deaths was 2.25 times greater than expected and 7.4 times greater than expected for lung cancer. Adenocarcinoma was the commonest histological type but other cell types were also increased. Finger clubbing (p less than 0.01) and percentage of predicted FEV1 (p less than 0.01) were of value in predicting death, but increasing profusion of small opacities greater than 1/0 (ILO/U-C international classification of radiographs of pneumoconiosis, 1971), duration of exposure to asbestos, time from first exposure to asbestos, and percentage of predicted vital capacity and transfer factor did not predict death.
Significance of finger clubbing in asbestosis. I.I. Coutts, J.C. Gilson, I.H. Kerr, et al. 1987;42(2):117-9. PubMed · Publisher · Free full text

Abstract

The prognostic significance of finger clubbing in asbestosis has been assessed in 167 cases certified by the London Pneumoconiosis Medical Panel from 1968 to 1974. Finger clubbing developed early in the clinical course of the disease and was associated with a lower gas transfer, a higher mortality and a greater likelihood of progression in intrapulmonary fibrosis than was found among cases without finger clubbing. Finger clubbing was not associated with heavier asbestos exposure. Its presence appears to be associated with a more severe form of disease.
Solitary fibrous tumour of the pleura: an ultrastructural and immunohistochemical study. S. Keating, G.T. Simon, I. Alexopoulou, et al. 1987;42(12):976-9. Case report PubMed · Publisher · Free full text

Abstract

Solitary fibrous tumour of the pleura is a benign neoplasm differing from diffuse pleural mesothelioma. It was originally thought to be a variant of mesothelioma because it consists of a spindle cell stroma associated with branching tubular structures lined by cuboidal cells. In this study of two cases the tubular structures were lined with ciliated and non-ciliated cuboidal cells. Ultrastructurally most of the non-ciliated cells had the features of type II pneumocytes, while the stromal cells had all the characteristics of fibroblasts. Immunohistochemical staining showed the epithelial cells to be positive for both keratin and carcinoembryonic antigen, whereas the stromal cells were negative. The findings support the theory that these tumours are fibroblastic in origin, and that the biphasic pattern is due to entrapment of non-neoplastic bronchiolar and alveolar epithelial cells.
Assessment of mineral fibres from human lung tissue. J.M. Davis, B. Gylseth, A. Morgan. 1986;41(3):167-75. Review PubMed · Publisher · Free full text

Summary

This review summarised the discussions and conclusions of an international workshop on technical problems in estimating the mineral fibre content of human lung tissue. The workshop was held in Oxford from 17 to 19 September 1984 and was sponsored by the North Atlantic Treaty Organisation and the British Asbestosis Research Council. Its aim was to make results from different laboratories more directly comparable. The authors noted that tissue blocks taken centimetres apart could give fibre counts differing by an order of magnitude. They suggested pooling several blocks from peripheral and central regions of the upper and lower lobes. They reviewed tissue digestion and ashing methods, sources of fibre loss and contamination, light and electron microscopic counting, the definition of a fibre (the 3:1 aspect ratio was retained), and fibre identification by electron diffraction and energy dispersive x ray analysis. They recommended that published work report standard reference points such as fibres longer than 5 µm, together with analytical sensitivity and detection limits. They discussed how fibrosis and the clearance and dissolution of chrysotile complicated relating fibre burden to asbestosis and mesothelioma, and the uncertain role of asbestos bodies. In a recent trial, seven laboratories analysed lungs from six asbestos-exposed individuals. The laboratories agreed well on which cases had high or low fibre levels, but their actual counts correlated poorly. The workshop recommended a three-stage international counting trial organised from Edinburgh.

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Diffuse pulmonary mesothelioma presenting as bilateral lymphangitis. A.P. Chahinian. 1986;41(3):223. Case report · Letter PubMed · Publisher · Free full text
Mineral fibres and mesothelioma. J.C. Wagner, F.D. Pooley. 1986;41(3):161-6. Editorial PubMed · Publisher · Free full text

Summary

In this editorial, the authors considered the evidence linking asbestos and other mineral fibres to diffuse mesothelioma of the pleura and peritoneum. They discussed four groups: commercial asbestos minerals; asbestos minerals as environmental contaminants (for example tremolite in talc, in chrysotile deposits and in agricultural soils); naturally occurring fibrous minerals such as erionite and absorbent clays; and man-made mineral fibres. They stated that the evidence linking crocidolite with mesothelioma was clear. Drawing on epidemiological, lung-tissue mineralogical and animal studies, some of them unpublished, they concluded that the fibres responsible for mesothelioma have a diameter of less than 0.25 µm and probably a length greater than 5 µm. Fine erionite fibres from Oregon produced mesotheliomas after inhalation in all cases, whereas no other fibre, including crocidolite, had produced tumours in more than 10% of cases. Early intrapleural experiments suggested that attapulgite, used as an asbestos substitute, might produce nearly as many mesotheliomas as the contaminated chrysotile it was replacing. Insulation wools showed no significant adverse effects in animals, but an extremely fine glass microfibre produced mesotheliomas. Mullite was the most common fibre found in human lung tissue. The authors concluded that any straight mineral fibre of the defined length and diameter must be regarded as a possible hazard. They also concluded that analysis of the fibres retained in the lungs, using transmission electron microscopy, was essential, because environmental dust studies could be misleading.

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Pathogenesis of pleurisy, pleural fibrosis, and mesothelial proliferation. A. Herbert. 1986;41(3):176-89. Review PubMed · Publisher · Free full text
Unilateral hyperhidrosis associated with underlying intrathoracic neoplasia. D.C. Lindsay, J.G. Freeman, C.O. Record. 1986;41(10):814-5. Case report PubMed · Publisher · Free full text

Summary

The authors reported two patients at the Royal Victoria Infirmary, Newcastle upon Tyne, in whom localised sweating on one side of the chest wall was associated with an intrathoracic tumour. The first, a 67-year-old retired shotblaster who smoked, had weight loss, mild breathlessness, right-sided chest pain and profuse sweating in a band at T6-9. A chest radiograph showed a large right pleural effusion, and pleural biopsy showed poorly differentiated carcinoma. The sweating continued for six months. He developed intra-abdominal metastases and died at home without necropsy. The second, a 58-year-old engineering foreman who smoked and had had a brief exposure to asbestos, had left chest ache, 12 kg weight loss and a large pleural effusion. Initial investigations, including pleural biopsy, were unhelpful. Six months later a band of sweating developed at T5-8 on the left, and left pleural mesothelioma was diagnosed clinically. He died four months later. Necropsy showed the left lung encased by mesothelioma invading the chest wall, with no metastases in the brain or spinal cord. The authors noted that nine cases with primary tumours, including one mesothelioma, and one with metastases had been reported since 1976. They discussed possible mechanisms, including irritation of nerves by tumour. They concluded that unilateral hyperhidrosis is usually a sign of advanced tumour spread and carries a poor prognosis.

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Asbestosis: assessment by bronchoalveolar lavage and measurement of pulmonary epithelial permeability. A.R. Gellert, J.A. Langford, R.J. Winter, et al. 1985;40(7):508-14. PubMed · Publisher · Free full text

Abstract

Thirty two patients with asbestosis were assessed by means of bronchoalveolar lavage (27 patients) and the half time clearance from lungs to blood (T1/2LB) of an inhaled aerosol of diethylenetriamine pentacetate (DTPA) labelled with technetium 99m (32 patients). T1/2LB was also measured in 20 non-smoking normal individuals and 17 smokers without a history of exposure to asbestos. Thirteen patients (46%) showed an increase in the percentage of neutrophils with or without an increase in the percentage of eosinophils and eight (29%) showed an increased percentage of lymphocytes. The number of neutrophils plus eosinophils expressed as a percentage of the total count was positively correlated with the length of the history of disease (r = 0.53, p less than 0.025) and greater percentages were associated with more severe impairment of lung function. Smokers had lower percentages of lymphocytes than non-smokers (p less than 0.002) and showed increased proportions of neutrophils and eosinophils more often than non-smokers (p less than 0.05). In 18 non-smokers with asbestosis the mean T1/2LB was 33.8 (range 10.0-62.0) minutes, significantly less than 57.2 (30.5-109) minutes in 20 non-smoking normal subjects (p less than 0.002). In non-smokers shorter T1/2LB correlated with a longer time since first exposure to asbestos (r = -0.65, p less than 0.005), longer duration of exposure (r = -0.70, p less than 0.001), and a shorter time since last exposure (r = 0.59, p less than 0.01). Shorter T1/2LB was also associated with increased inflammatory activity as shown by higher bronchoalveolar lavage cell counts (r = -0.53, p less than 0.025) and higher combined percentages of neutrophils, eosinophils, and lymphocytes (r = -0.47, p less than 0.05). The techniques of bronchoalveolar lavage and measurement of inhaled solute clearance may be useful in assessing inflammatory activity in asbestosis.
Comparison of tumour markers in malignant mesothelioma and pulmonary adenocarcinoma. A.R. Gibbs, R. Harach, J.C. Wagner, et al. 1985;40(2):91-5. PubMed · Publisher · Free full text

Abstract

Immunohistological methods were used to investigate the presence of carcinoembryonic antigen, beta 1 pregnancy specific glycoprotein, beta subunit of human chorionic gonadotrophin, human placental lactogen, calcitonin, and keratin in formalin fixed tissue from 29 malignant mesotheliomas and 27 pulmonary adenocarcinomas. Malignant mesotheliomas were negative for tumour markers except for the beta subunit of human chorionic gonadotrophin and keratin, one and 13 cases respectively being positive for these. Pulmonary adenocarcinomas, however, were frequently positive for tumour markers--namely, carcinoembryonic antigen, beta 1 pregnancy specific glycoprotein, beta subunit of human chorionic gonadotrophin, human placental lactogen, calcitonin, and keratin. The presence of carcinoembryonic antigen and beta 1 pregnancy specific glycoprotein within an intrathoracic tumour is strong evidence against its being of mesothelial origin.
Exogenous particles in lymph nodes in patients with shrinking pleuritis with atelectasis. L. Dernevik. 1985;40(12):948-51. PubMed · Publisher · Free full text

Abstract

Shrinking pleuritis with atelectasis is a disease in which a compression atelectasis of the lung is caused by shrinking of the inflamed visceral pleura. This reaction has been attributed to asbestos. By means of scanning electron microscopy, with computerised x ray spectrophotometry and x ray diffraction analysis, tissue samples from the lymph nodes of patients with the disease and control subjects were examined for other particles of possible aetiological importance. The results would suggest, however, that asbestos is the most important factor in the aetiology of shrinking pleuritis with atelectasis.
Open lung biopsy in patients with diffuse pulmonary shadowing. G.E. Venn, P.H. Kay, C.J. Midwood, et al. 1985;40(12):931-5. PubMed · Publisher · Free full text

Abstract

The radiological appearances of diffuse pulmonary shadowing are not specific and frequently histological examination is necessary to provide a diagnosis or assess the activity of the disease. From July 1979 to May 1983 open lung biopsy was performed in 101 patients through a limited submammary incision. Twenty seven patients had undergone prior invasive investigations and 27 were taking corticosteroids at the time of biopsy. In 92 patients the histological appearances after open lung biopsy were sufficiently specific to permit diagnosis. Respiratory tract infection occurred in six patients and in eight there was some superficial infection of the wound. These complications were more frequent in patients taking corticosteroids but the difference was not statistically significant. The chest drain was removed usually on the first postoperative day. In three critically ill patients an air leak occurred after removal of the drain, requiring formal surgical re-exploration and drainage in two cases and a brief period of intercostal drainage in the third. Four patients in the series died. All had severe pre-existing lung disease; in three open lung biopsy was performed in the late stages of severe, rapidly progressive lung disease eluding diagnosis; the fourth patient, who had massive pulmonary fibrosis from asbestos lung disease, developed a respiratory tract infection and died from progressive respiratory failure. Open lung biopsy can be performed with minimal morbidity and a high diagnostic yield. The approach used in this series provides a safe and reliable operation with good cosmetic results.
Pleural mesothelioma treated by fast neutron therapy. P.R. Blake, M. Catterall, P.A. Emerson. 1985;40(1):72-3. Case report PubMed · Publisher · Free full text

Summary

The authors reported a single patient with malignant pleural mesothelioma treated with fast neutron therapy at the Medical Research Council Cyclotron Unit, Hammersmith Hospital, London. A 56 year old housewife presented in January 1976 with a persistent cough and a small pleural effusion. Pleural biopsy and bronchoscopy showed no malignancy. In April 1977 a subcutaneous mass appeared at the biopsy site, and its excision showed malignant mesothelioma, confirmed by electron microscopy. By July 1977 there was further local recurrence, and computed tomography showed a 45 x 50 mm left paravertebral mass. She had no history of asbestos exposure, and there was no evidence of distant metastases. In July and August 1977 she received 1650 cGy of fast neutrons in 12 fractions over 35 days. Over the next four months the subcutaneous mass regressed completely. A 10 x 10 mm nodule that grew next to the treated area in March 1978 regressed after cobalt radiation. The effusion needed five aspirations and then did not recur. At 78 months after treatment there was no sign of recurrent disease. The authors noted that the low energy of the Hammersmith neutron beam limited treatment to thin patients with limited disease. They concluded that the long disease free survival was encouraging. They suggested that higher energy cyclotrons could allow radical treatment of larger or deeper mesotheliomas and comparison with x ray treatment.

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Asbestos related pleuropulmonary lesions and the erythrocyte sedimentation rate. G. Hillerdal. 1984;39(10):752-8. PubMed · Publisher · Free full text

Abstract

Asbestos related lesions of the lung parenchyma and the pleura can be divided into three main types: parietal pleural plaques, diffuse interstitial fibrosis ("classical asbestosis"), and a third type of reaction affecting both the pleura and the lung parenchyma. The last type includes such lesions as acute pleurisy, diffuse pleural thickening, and rounded atelectasis. Among 1344 patients with asbestos related pleural lesions, 1190 had pleural plaques, 29 of whom also had pulmonary fibrosis (asbestosis); 83 had unilateral sequelae of pleurisy, of whom nine had asbestosis; and 71 had bilateral sequelae of pleurisy, of whom 23 also suffered from asbestosis. The erythrocyte sedimentation rate (ESR) was measured in 184 patients--79 with pleural plaques, 44 with unilateral sequelae of pleurisy, and 61 with bilateral sequelae. In patients with pleural plaques with or without asbestosis the ESR was usually normal, the mean being 9.6 mm in one hour. Among patients with sequelae of pleurisy, however, many had a raised ESR. The mean ESR was 25.7 mm in one hour in those with bilateral changes and 13.2 in those with unilateral changes. Statistical analysis showed that in this group of subjects the presence of sequelae of pleurisy was a highly significant determining factor for the ESR (p less than 0.0001). Asbestosis alone was not a significant determining factor but there was a low grade of significance for the combined effect of asbestosis and sequelae of pleurisy (p less than 0.05). These findings suggest that the pathogenesis of the various changes is different.
Diffuse pleural thickening in asbestos workers: disability and lung function abnormalities. C.R. McGavin, G. Sheers. 1984;39(8):604-7. PubMed · Publisher · Free full text

Abstract

Data from 37 asbestos workers with diffuse pleural fibrosis have been analysed. None had radiological evidence of asbestosis or physiological evidence of airflow obstruction. Forty per cent had breathlessness of MRC grade 3 or higher. Vital capacity was significantly lower in the subjects in the higher grades of breathlessness and in those with greater radiographic pleural abnormality. No relationship was demonstrated between dust exposure and either radiographic abnormality or grade of breathlessness. Diffuse pleural thickening, particularly when extensive and bilateral, causes functional impairment and disability.
Malignant mesothelioma of the pleura: a study of 52 treated and 64 untreated patients. M.R. Law, A. Gregor, M.E. Hodson, et al. 1984;39(4):255-9. PubMed · Publisher · Free full text

Abstract

We have carried out sequential prospective studies of treatment with surgery alone, chemotherapy, and radiotherapy in malignant mesothelioma of the pleura. The survival of treated patients was contrasted with that of 64 contemporary untreated patients whose clinical condition at presentation was comparable with that of the treated patients. Non-radical surgery alone (28 patients) was of palliative benefit, particularly for the control of recurrent pleural effusions, and may have prolonged survival in one patient with localised malignant mesothelioma. Chemotherapy with doxorubicin, vincristine, and cyclophosphamide (12 patients, with preceding surgery in eight) was without objective benefit. Megavoltage radiotherapy by an off axis beam rotational technique (12 patients, with preceding surgery in eight) abolished pain and dyspnoea and may have prolonged survival in one patient and terminated recurrent pleural effusions in three, but it was of no value in the other patients. There was no significant difference in survival between treatment groups or between treated and untreated patients, and no difference when mesotheliomas of epithelial, sarcomatous, and mixed cell types were examined separately. Treatment of this disease appeared to fail because of the unresponsiveness of the tumour to existing forms of treatment and the advanced stage of the disease at clinical presentation.
Mast cells and inhalation of asbestos in rats. M.M. Wagner, R.E. Edwards, C.B. Moncrieff, et al. 1984;39(7):539-44. PubMed · Publisher · Free full text

Abstract

Mast cell counts were performed on sections taken from the lungs of rats exposed by inhalation to different UICC samples of asbestos fibres for periods ranging from a few days to two years. A comparison of mast cell counts with grades of fibrosis showed that there is a sevenfold increase when there is interlobular linking of the fibrotic lesions (grade 5). Submesothelial mast cells showed a trend of increasing numbers with increasing exposure and with increasing subpleural thickening. Each type of asbestos produced a steady increase in mast cell numbers with increasing exposure. Two samples from animals exposed to chrysotile and two from animals exposed to amphiboles (crocidolite and amosite respectively) had 10 times as many cells as the control group after six and 24 months' exposure. Another amphibole, anthophyllite, produced 50 times more cells than were present in the control specimen appropriate for the heaviest exposure. These results are briefly discussed in relation to further exposure, smoking, and characteristics of the dusts.
Pleural mesothelioma and the syndrome of inappropriate secretion of antidiuretic hormone. N.M. Siafakas, K. Tsirogiannis, B. Filaditaki, et al. 1984;39(11):872-3. Case report PubMed · Publisher · Free full text

Summary

The authors, from the Departments of Thoracic Medicine and Histopathology at Evangelismos Hospital, Athens, Greece, described a case of malignant pleural mesothelioma associated with the syndrome of inappropriate secretion of antidiuretic hormone. They stated that only one such case had been reported before. The patient was a 58 year old man with a five month history of pain in the upper right chest and right shoulder, followed by low grade fever and a dry cough. He had worked as a clerk in the city and had no apparent exposure to asbestos. He was a former smoker. Chest radiographs showed lobulated peripheral shadows in the upper right chest. At thoracotomy there was extensive diffuse thickening of the parietal pleura with plaque formation. Biopsy showed a biphasic malignant mesothelioma. Electron microscopy found secretory granules of 70 to 100 nm in the tumour cells. He received no treatment. A month later he was readmitted with fever and confusion. Serum sodium was 122 to 128 mmol/l and plasma osmolality 258 mosmol/kg, against a urine osmolality of 390 mosmol/kg. Urinary sodium excretion was 196 mmol/24 h. Serum arginine vasopressin was 15 pg/ml (normal 4-8 pg/ml). Fluid restriction failed, and he died 27 days after admission. No necropsy was performed. The authors concluded that the tumour cells might produce, store and release antidiuretic hormone or a similar substance. They considered that their case supported an earlier suggestion that mesothelioma may often be accompanied by this syndrome.

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Rarity of mineral fibre pleurisy among persons exposed to Finnish anthophyllite and with low risk of mesothelioma. G. Hillerdal, A. Zitting, A.H. van Assendelft, et al. 1984;39(8):608-11. PubMed · Publisher · Free full text

Abstract

Endemic pleural plaques are reported from many parts of the world. In Central Europe and in Finland no connection with malignant mesotheliomas has been found, whereas this tumour is often encountered in areas in Turkey where endemic plaques also occur. There seem, however, to be differences in the radiological appearances found in these areas. In the present study chest radiographs of 317 persons with pleural plaques from the endemic area of Finland were scrutinized. It was found that 4.7% showed a blunted costophrenic angle unilaterally and 0.9% bilaterally. The prevalence of sequelae of pleurisy is statistically very highly significantly lower than in people with pleural plaques in Turkey. As the risk of mesothelioma appears to be low in Finland, the results are in accordance with the hypothesis that the risk of mesothelioma in a given population is higher if in that population there is a high incidence of benign asbestos pleurisy.
The pathology of asbestos related disease. J.M. Davis. 1984;39(11):801-8. Review PubMed · Publisher · Free full text

Summary

This review summarised the main conclusions of a symposium on the pathology of asbestos related disease held in Edinburgh on 27 and 28 April 1983. It was attended by British research workers, hospital pathologists, and doctors from the pneumoconiosis medical panels and the asbestos industry. Four topics were covered: lung dust burden and disease, the diagnosis of mesothelioma, present day patterns of asbestosis, and medicolegal attribution of disease to asbestos. Expressed as phase contrast equivalents, fibre counts ranged from 5000 to 100 000 per gram of dried lung in controls without industrial exposure, from 20 000 upwards in mesothelioma, and from below 1 000 000 to 50 000 000 in mild asbestosis. Amphibole counts, but not chrysotile counts, appeared related to asbestosis severity and to mesothelioma. The participants called for standardised techniques and accredited laboratories, and regarded electron microscopy as essential for people exposed only to chrysotile. Histological, staining, cytological and electron microscopic criteria for mesothelioma were described. About 5-10% of the 500 annual UK cases were thought to present serious diagnostic difficulty at necropsy. The classical pattern of advanced asbestosis was now rarely seen in Britain, and a four-grade histological scale was outlined. Opinions differed on whether 1 000 000 or 250 000 fibres per gram (phase contrast) marked the level below which fibrosis was unlikely. Many pathologists favoured apportioning causality rather than an "all or nothing" approach.

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Assessment of progression of asbestosis in the sheep model by bronchoalveolar lavage and pulmonary function tests. R. Bégin, M. Rola-Pleszczynski, S. Massé, et al. 1983;38(6):449-57. PubMed · Publisher · Free full text

Abstract

To study the relationship between the results of bronchoalveolar lavage and pulmonary function tests during induction and progression of asbestosis, three groups of six sheep were exposed repeatedly by intratracheal injection to either saline (controls), low doses of Canadian chrysotile UICC asbestos (cumulative exposure 328 mg) (low-dose group), or high doses of the same fibres (cumulative dose 2282 mg) (high-dose group) until there was clear evidence of alveolitis from the lung biopsy specimens of all sheep of the high-dose group. During the course of this induction and for the following eight months lung biopsies, bronchoalveolar lavage and pulmonary function tests were performed at two-month intervals. At the time of initial alveolitis in the high-dose group there was no significant change in the cellularity of the bronchoalveolar lavage fluid, but static lung compliance (Cst), vital capacity (VC), arterial oxygen tension (Pao2), and diffusion capacity (DL/VA) were significantly lower than in the other groups. In the following months, as the alveolitis evolved into a fibrosing process, macrophages and neutrophils from the bronchoalveolar lavage fluid increased significantly and pulmonary function deteriorated. Proteins and enzymes in the bronchoalveolar lavage fluid also increased significantly in the high-dose group. These data show that in the sheep model of asbestosis simple tests of pulmonary function correlate well with histological changes and changes in the bronchoalveolar lavage fluid in the course of the disease and can be used to assess progression of asbestosis.
Evidence for longer survival of patients with pleural mesothelioma without asbestos exposure. M.R. Law, F.G. Ward, M.E. Hodson, et al. 1983;38(10):744-6. PubMed · Publisher · Free full text

Abstract

In a group of 23 patients with histologically confirmed malignant mesothelioma of the pleura who could not recall exposure to asbestos dust, survival was significantly longer than in a group of 83 patients with known exposure. Asbestos bodies were found by a quantitative method significantly less frequently in the unexposed than in the exposed group. The longer survival of patients without known exposure could not be correlated with any significant difference in the histological cell types of the tumours from those of exposed patients. In the 83 patients with known exposure survival did not relate to duration of exposure. Consequently, although the tumours of patients unable to recall exposure may be caused by unrecognised environmental contamination with asbestos dust, the longer survival of these patients would suggest a different aetiology.
Mineralogical analysis of bronchoalveolar lavage fluid as an aid to diagnosis of "imported" pleural asbestosis. P. De Vuyst, M. Mairesse, A. Gaudichet, et al. 1983;38(8):628-9. Case report PubMed · Publisher · Free full text

Summary

The authors reported an "imported" case of pleural disease related to non-occupational asbestos exposure, in which the diagnosis was established by bronchoalveolar lavage. The patient was a 57-year-old Turkish woman referred in Belgium for investigation of bilateral pleural thickening. She was born in Karakalar in the Afyon area of Anatolia and had lived in Belgium for 23 years. She had never worked, had never smoked and had no remarkable respiratory symptoms. The chest radiograph showed bilateral nodular pleural thickening with diaphragmatic calcification. Lung function tests showed a mild obstructive defect with normal gas transfer. An open pleural biopsy showed hyaline plaques on the parietal pleura, with no signs of mesothelioma or of asbestos fibres. A 25 ml sample of lavage fluid was digested, filtered and examined by optical microscopy, which found typical asbestos bodies in large numbers (117 per ml of fluid). Transmission electron microscopy with energy-dispersive x-ray analysis identified the fibres as tremolite asbestos (MgO 21%, SiO2 52%, CaO 16%, FeO 10%). No erionite was found. The authors concluded that lavage confirmed the diagnosis of benign pleural asbestosis. They noted that in their experience such a result had been found only in people with definite asbestos exposure. They also noted that tremolite occurs in the soil around Afyon, where local asbestos-containing material is used for home construction and whitewashing.

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In plain English

This is a case report about one patient in Belgium. A 57-year-old Turkish woman was born in Karakalar in the Afyon area of Anatolia and had lived in Belgium for 23 years. She had never worked and had never smoked. She was referred because of thickening of the pleura (the lining around the lungs) on both sides. Her chest X-ray showed nodular pleural thickening on both sides, with calcification on the diaphragm. She had no notable breathing symptoms. Lung function tests showed a mild obstructive defect and normal gas transfer. A biopsy showed hyaline plaques on the outer (parietal) pleura, with no signs of mesothelioma. Fluid washed from her lungs during bronchoscopy (bronchoalveolar lavage) contained 117 asbestos bodies per ml. Electron microscope analysis identified the fibres as tremolite asbestos, and no erionite was found. The authors described her pleural disease as related to non-occupational asbestos exposure. They concluded that the lavage analysis confirmed the diagnosis of benign pleural asbestosis. As a single case, it provides no rate of disease.

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Radiological study of pleural changes in relation to mesothelioma in Turkey. G. Hillerdal, Y.I. Baris. 1983;38(6):443-8. PubMed · Publisher · Free full text

Abstract

In some villages in central Turkey pleural changes occur as a result of environmental exposure to mineral fibres. In most cases the fibre is asbestos but in some cases the non-asbestos fibre erionite, a zeolite, is responsible. The incidence of malignant mesothelioma is much higher in "erionite villages" than in "asbestos villages" despite similar frequencies of pleural changes. In this study chest radiographs from 466 people from asbestos villages, 549 from erionite villages, and 382 controls were compared. The frequency of pleural calcification was about the same in the two groups of villages studied, but the minor fissures were visible to a greater degree in erionite cases. In people from erionite villages "atypical" pleural calcification, due to calcification of the visceral rather than the parietal pleura, was more common. These differences may indicate that the fibres have different lengths and diameters.
Interpretation of pleural biopsy specimens and aspirates with the immunoperoxidase technique. A. Herbert, P.J. Gallagher. 1982;37(11):822-7. PubMed · Publisher · Free full text

Abstract

In pleural biopsy specimens and histological sections from the fibrin clots of pleural fluid aspirates it may be difficult to distinguish reactive mesothelial cells from malignant mesothelial cells and metastatic carcinoma. Reactive pleurisy with effusion is usually associated with loss of cohesion and exfoliation of mesothelial cells, which is consistent with the hypothesis that they act as facultative histiocytes. A series of biopsy specimens and sections of clots from benign and malignant pleural effusions have been stained by the immunoperoxidase technique for the histiocytic markers alpha 1-antitrypsin, alpha 1-antichymotrypsin, and lysozyme (muramidase). Eight cases of mesothelioma were included. Mesothelial cells when seen as a monolayer lining the pleural surface were negative. Reactive mesothelial cells, usually seen as exfoliated cells, were consistently strongly positive for alpha 1-antichymotrypsin and more variably for alpha 1-antitrypsin and lysozyme. Malignant cells, whether from carcinoma or from mesothelioma, were usually but not always negative. Consequently immunohistochemical staining for alpha 1-antichymotrypsin is often helpful in distinguishing reactive mesothelial cells from malignant cells.
Malignant mesothelioma of the pleura: relation between histological type and clinical behaviour. M.R. Law, M.E. Hodson, B.E. Heard. 1982;37(11):810-5. PubMed · Publisher · Free full text

Abstract

The differing clinical behaviour of malignant mesothelioma of different cell types was studied in 115 cases of pleural mesothelioma, classified histologically into epithelial (60), sarcomatous (25), and mixed (30). Epithelial mesotheliomas were associated with clinical features characteristic of carcinomas rather than sarcomas, including spread of tumour by direct extension, large pleural effusions, contralateral pleural effusions, ascites, metastases in regional lymph nodes, and occasional response to radiotherapy. Sarcomatous mesotheliomas were associated with clinical features more characteristic of sarcomas, with more frequent distant metastases, little or no effusion, and shorter survival. Mixed tumours had features of both, large pleural effusions occurring as frequently as with epithelial tumours, but survival being almost as poor as in sarcomatous cases. Despite these differences there is evidence from published reports that epithelial, sarcomatous, and mixed mesotheliomas have a common origin from mesothelial cells or their precursor cells.
Pleural biopsy in the diagnosis of malignant mesothelioma. A. Herbert, P.J. Gallagher. 1982;37(11):816-21. PubMed · Publisher · Free full text

Abstract

In an attempt to distinguish reactive from neoplastic mesothelial proliferation, the histological material and clinical records of 153 patients on whom open or closed pleural biopsies were performed during 1976 were reviewed. In six of the 10 patients subsequently shown to have malignant mesothelioma the specimens from closed pleural biopsy had been reported as negative or equivocal but in retrospect showed changes not observed in reactive pleurisy. These included papillary mesothelial proliferation, exfoliated papillae, sheets of atypical mesothelial cells, and abnormal fibroblastic proliferation. In contrast, in inflammatory conditions the mesothelial lining was usually replaced by granulation tissue, although sheets or clumps of exfoliated mesothelial cells were often present in the corresponding pleural fluid clot. Some multilayering of parietal mesothelium was occasionally seen in chronic pleurisy and around metastases.
Pulmonary asbestos and dust content in East Anglia. P.G. Stovin, P. Partridge. 1982;37(3):185-92. PubMed · Publisher · Free full text

Abstract

Measurements were made of the asbestos fibre and dust content of samples from 96 surgically excised lungs; 42 necropsies on patients with lung cancer, 11 necropsies on patients with non-pulmonary malignancies, and 59 necropsies on patients without any malignant disease. The patients' ages ranged from 45 to 74 years at the time of study. None of the patients had asbestosis. The distribution of fibres and dust content of the lungs showed a log-normal distribution. There was no significant difference in fibre counts or dust content between men and women, and between lung cancer and non-cancer patients. The only group with an association with a high asbestos fibre count was four necropsy cases of pleural mesothelioma. There was no significant relationship between asbestos fibre count and dust content of the lung. The present data suggest that asbestos fibre counts below 100,000 per gram of dried lung are not related to specific asbestos disease, although in the surgical cases who were closely questioned on their residential and occupational histories most of those with fibre counts above 30,000 per gram dried lung had had occasions of definite or very likely asbestos exposure.
Role of alveolar macrophages in asbestosis: modulation of neutrophil migration to the lung after acute asbestos exposure. C.I. Schoenberger, G.W. Hunninghake, O. Kawanami, et al. 1982;37(11):803-9. PubMed · Publisher · Free full text

Abstract

After intratracheal injection of short chrysotile asbestos fibres in guinea-pigs an intense neutrophil alveolitis was observed within three days. Evaluation by bronchoalveolar lavage of the inflammatory and immune effector cells producing the alveolitis by three days showed an increased proportion of polymorphonuclear leucocytes, which comprised 21% +/- 3% of the total leucocytes compared with 9% +/- 2% for the controls (p less than 0.05), persisting for at least six weeks (after which time the polymorphonuclear leucocytes comprised 28% +/- 2% compared with 7% +/- 1% for the controls: p less than 0.05). One mechanism by which asbestos fibres may cause polymorphonuclear leucocytes to be attracted to the alveolar structures is by induced release of neutrophil chemotactic factor by alveolar macrophages. When exposed in vitro to short or intermediate chrysotile fibres or amosite or crocidolite fibres guinea-pig alveolar macrophages released appreciable amounts of neutrophil chemotactic factor. The release of this chemotactic factor was augmented when the asbestos fibres had been previously exposed to normal serum. The chemotactic factor was lipid soluble, and was similar to the neutrophil chemotactic factor spontaneously released by alveolar macrophages recovered from guinea-pigs exposed in vivo to short chrysotile fibres. These observations suggest that alveolar macrophages may play an important part in the early stages of asbestosis by modulating the migration of neutrophils to the lung.
Asbestos and public health. D. Liddell. 1981;36(4):241-4. PubMed · Publisher · Free full text

Summary

This editorial summarised evidence on asbestos and health, concentrating on mortality, especially from lung cancer. The author drew heavily on a Quebec cohort of 10 939 men and 440 women who had worked at least a month in chrysotile mining and milling, some from 1904. They were followed to the end of 1975, with nearly 4500 deaths, and the study had job-by-job dust estimates and smoking histories. In Quebec the exposure-response relationship for lung cancer was effectively linear, and the author saw no evidence for a threshold or 'safe' dose. Most studies supported a 'fibre gradient': crocidolite had the most severe health effects, chrysotile the least, and amosite fell in between. The gradient was steepest for mesothelioma. The author considered that one new study of chrysotile textile workers, out of line with earlier reports, needed careful evaluation. He stated that current control limits for chrysotile were equivalent in carcinogenic potency to smoking three or four cigarettes a week. On a very gloomy interpretation of Rochdale factory data, 50 years' exposure at the UK limit of 1 f/ml would lead to 1.25% excess mortality from lung cancer. He recommended treating amosite like crocidolite and urged care when removing asbestos from buildings. He noted that no ill effects had been shown from asbestos in drinking water, food or the general atmosphere, and that substitutes resembling asbestos might be similarly harmful.

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Benign asbestos pleural effusion: diagnosis and course. B.W. Robinson, A.W. Musk. 1981;36(12):896-900. PubMed · Publisher · Free full text

Abstract

We have reviewed 22 patients with benign asbestos pleural effusion seen over a 17-year period. The mean duration of exposure to asbestos was 5.5 years and the mean interval between exposure and presentation was 16.3 years. In five the effusion was asymptomatic. Fever was uncommon but in 15 of 21 patients the ESR was elevated. Leucocytosis was noted in seven of 20 patients. Autoantibodies were rarely detected. The pleural fluid was usually blood-stained and the volume aspirated was rarely larger than 500 ml. Pleural biopsies revealed established pleural fibrosis and/or inflammatory infiltration with fibrinous exudate and mesothelial and fibroblastic proliferation. A positive mantoux test was noted in eight of 12 patients but there was no other evidence of tuberculosis. The mean duration to spontaneous resolution of the effusion was 4.3 months. During a follow-up period of 28.1 years from initial exposure to asbestos (mean 22.8 years) and up to 17.2 years from initial presentation with a pleural effusion (mean 6.3 years) seven patients had a single recurrence and only one patient had multiple pleural effusions. Only three patients experienced persistent pleural pain. It was not possible to predict the likelihood of recurrence of an effusion or the persistence of pleural pain from the data at presentation. No patient subsequently developed mesothelioma or other neoplasm.
Non-malignant asbestos pleural disease. G. Hillerdal. 1981;36(9):669-75. PubMed · Publisher · Free full text

Abstract

During a 10-year period (1970-79) all patients in Uppsala County found to have pleural changes related to asbestos exposure were followed. The lesions could be divided into four types: parietal pleural plaques, exudative pleurisy, thickening of the visceral pleura, and progressive pleural fibrosis. There were 891 cases. The most common type was parietal plaques, which was seen in 827 patients, some of whom later developed other changes. In 22 types exudation was proven radiologically, and in 84 more cases obliteration of the costo-phrenic angle was seen. The exudations almost all had a benign course, despite sometimes fairly large and bloody effusions. They were practically all symptom-free, being a surprise finding on chest radiography. Thickening of the visceral pleura can only be seen radiologically in the fissures and occurred in a few cases in addition to other changes. In a small group of more heavily exposed individuals, a progressive pleural fibrosis developed, sometimes after an initial effusion.
Reactive mesothelial proliferation: a necropsy study. C.D. Sheldon, A. Herbert, P.J. Gallagher. 1981;36(12):901-5. PubMed · Publisher · Free full text

Abstract

To establish a histological standard against which surgical biopsy material could be compared, the degree of mesothelial proliferation was studied in 100 unselected necropsies. A minor degree of mesothelial hyperplasia was identified in 10 cases, usually close to areas of fibrous adhesions. Pleural plaques were present in 33 patients but there was no evidence of associated mesothelial proliferation. No mesothelial changes were noted in patients with empyema or pleural metastases. These findings indicated that the degree of mesothelial hyperplasia in common disorders of the pleura is relatively slight. Significant mesothelial proliferation in needle biopsies should therefore be viewed with considerable suspicion and, where clinically appropriate, be followed by further investigation.
Bronchoalveolar lavage in pulmonary fibrosis: comparison of cells obtained with lung biopsy and clinical features. P.L. Haslam, C.W. Turton, B. Heard, et al. 1980;35(1):9-18. PubMed · Publisher · Free full text

Abstract

Bronchoalveolar lavage, open lung biopsy, and cell extraction from the biopsy material have been studied in 21 symptomatic patients with progressive pulmonary fibrosis (18 with cryptogenic fibrosing alveolitis, fulfilling also the criteria for “usual interstitial pneumonia” (UIP), and three with rapidly progressive disease probably related to asbestos exposure). The total and differential cell counts between the three different samples have been compared as well as the influence on them of smoking and their correlation with steroid responsiveness and later progress. There was no correlation between semiquantitative scores of cell types observed within alveolar spaces and in alveolar walls and the differential or total cell counts obtained from extraction or lung lavage samples. There was, however, some correlation between differential counts obtained from lung lavage and extractions (neutrophils p<0·02, eosinophils p<0·07, lymphocytes p<0·08) suggesting that lung lavage reflects the cellularity of the peripheral parts of the lung in patients without overt bronchial disease. Steroid responsiveness related to the percentage of lymphocytes found in extraction samples (p<0·01) and was associated with a complementary fall in the percentage of macrophages (p<0·02). There was no relationship between steroid response and the numbers of neutrophils or eosinophils in extracted samples. There was a trend towards increased numbers of lymphocytes in the lung wash in those patients responding to steroids. Those cases showing more rapid progression before starting treatment tended to have higher percentages of lymphocytes, neutrophils, or eosinophils in the lung lavage than more slowly deteriorating cases (p<0·01). Follow-up studies showed that three cases having predominant lymphocytes in the lung lavage continued to do well while nine cases with predominant neutrophils or eosinophils or both showed a less satisfactory response to steroids and often deteriorated. Differential cell counts from biopsy extractions and lung lavage may give information additional to conventional light microscopy on the likelihood of steroid responsiveness as well as providing some measure of the activity of disease.
Mesotheliomas, minerals, and man-made mineral fibres. P.C. Elmes. 1980;35(8):561-3. PubMed · Publisher · Free full text

Summary

In this editorial, the author reviewed the evidence available in 1980 on which mineral fibres cause mesothelioma and noted that no clear advice could yet be given on its prevention. South African evidence had been consistent with the view that only crocidolite causes mesothelioma. No mesotheliomas had occurred in the Finnish anthophyllite mining area, although a high proportion of the population developed pleural plaques. A few more cases than expected had been reported in the Canadian chrysotile mining area, where crocidolite had been processed during the 1939-45 war and some chrysotile is contaminated with tremolite. Among British and Canadian gas mask workers, all but one of the 100 or more cases arose among those making military masks with crocidolite filters. Civilian masks contained chrysotile. Because mesothelioma has an average latent interval of about 40 years and exposure records are scanty, the author discussed lung fibre analysis by optical and electron microscopy. He noted that chrysotile fibres probably break up and dissolve in the tissue. Animal injection experiments suggested that potency relates to fibre size and shape rather than fibre type. Studies of rock, wool and glass fibre workers had not confirmed this concern. The author also described mesotheliomas in Turkey linked to erionite and tremolite. He concluded that reliance would have to be placed on animal and cell-culture tests.

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Pleural calcification, pleural mesotheliomas, and bronchial cancers caused by tremolite dust. S. Yazicioglu, R. Ilçayto, K. Balci, et al. 1980;35(8):564-9. PubMed · Publisher · Free full text

Abstract

Around the town of Cermik in south-east Turkey there are many deposits of asbestiform minerals, some of which are used to make whitewash or stucco. A sample of 7000 of the population revealed 461 (6.5%) with pleural thickening and calcification, of whom 103 (1.47% of the total) had evidence of interstitial pulmonary fibrosis. Forty-one patients with respiratory cancer were admitted to the Diyarbakir Chest Hospital from around Cermik and from a comparable area of equal population (but without asbestos deposits) in 1977-8. Of these 23 were mesotheliomas, 22 coming from around Cermik. In addition, 11 of the 18 primary bronchial cancers came from around Cermik. A similar excess of mesothelioma and bronchial cancer had been admitted from the Cermik area in previous years. The whitewash or stucco material has been shown to contain fibrous tremolite and non-fibrous antigorite/lizardite, chlorite, and talc. A lung biopsy of a patient from Cermik contained large numbers of tremolite fibres, both free and forming asbestos bodies. There were only occasional chrysotile fibres.
Respiratory function changes after asbestos pleurisy. P.H. Wright, A. Hanson, L. Kreel, et al. 1980;35(1):31-6. Case report PubMed · Publisher · Free full text

Abstract

Six patients with radiographic evidence of diffuse pleural thickening after industrial asbestos exposure are described. Five had computed tomography of the thorax. All the scans showed marked circumferential pleural thickening often with calcification, and four showed no significant evidence of intrapulmonary fibrosis (asbestosis). Lung function testing showed reduction of the inspiratory capacity and the single-breath carbon monoxide transfer factor (TLCO). The transfer coefficient, calculated as the TLCO divided by the alveolar volume determined by helium dilution during the measurement of TLCO, was increased. Pseudo-static compliance curves showed markedly more negative intrapleural pressures at all lung volumes than found in normal people. These results suggest that the circumferential pleural thickening was preventing normal lung expansion despite abnormally great distending pressures. The pattern of lung function tests is sufficiently distinctive for it to be recognised in clinical practice, and suggests that the lungs are held rigidly within an abnormal pleura. The pleural thickening in our patients may have been related to the condition described as "benign asbestos pleurisy" rather than the interstitial fibrosis of asbestosis.

1970s

Correspondence. A.J. Roncoroni. 1979;34(3):430. Letter PubMed · Publisher · Free full text
Pleural effusion: laboratory tests in 300 cases. A. Hirsch, P. Ruffie, M. Nebut, et al. 1979;34(1):106-12. PubMed · Publisher · Free full text

Abstract

The cause of pleural effusion was studied in 300 consecutive patients by clinical examination and laboratory tests. The three most common causes were found to be cancer 117 cases (metastatic 65, bronchogenic 34, mesothelioma 10, lymphoma 7, other 1); tuberculous infection 53; and bacterial infection 38. The cause was not found in 62 patients. Cancer diagnosis was established by cytological examination of pleural fluid (63), closed pleural biopsy (37), and open pleural biopsy (11). Tuberculosis was diagnosed by culture of pleural fluid (12), closed pleural biopsy (38), and open pleural biopsy (3). In cases of empyema 12 Gram-positive and two Gram-negative cocci and two anaerobes were identified. The various causes and the usefulness of the different investigative procedures are discussed, and the data evaluated in the light of current knowledge about mechanisms of transfer through the pleural space.
Rheumatoid "pneumoconiosis" (Caplan's syndrome) in an asbestos worker: a 17 years' follow-up. I.A. Greaves. 1979;34(3):404-5. Case report PubMed · Publisher · Free full text

Summary

This report described the later clinical course and necropsy findings of a man first reported by Tellesson in 1961 as having rheumatoid pneumoconiosis (Caplan's syndrome) related to asbestos exposure. In 1959 the patient, then 39, had worked for 15 years in an asbestos cement factory. He had no further asbestos exposure after 1957. Chest radiographs showed lung nodules. These were resected at thoracotomy in June 1959 and showed histology considered typical of rheumatoid pneumoconiosis, with asbestos bodies within the nodules and interstitial fibrosis. Rheumatoid arthritis, absent at thoracotomy, developed within 12 months. Further nodules appeared in both lungs, some cavitating, with no new lesions after 1964. Corticosteroid treatment in 1962 was followed by severe infection and lifelong chronic sputum production. Pleural calcification increased over time. He later developed splenomegaly, neutropenia, anaemia, leg ulcers, thyrotoxicosis, several circulating autoantibodies, and renal impairment. He died suddenly in 1976 after a myocardial infarction. At necropsy the pleura was thickened, fibrosed and calcified, and both lungs contained nodules 0.5 to 5 cm in diameter. Occasional ferruginous fragments but no typical asbestos bodies were seen, and there was no diffuse fibrosis attributable to asbestosis. The author concluded that asbestos exposure was possibly of little importance in the development of the nodules. He suggested that the patient's multiple immune-related diseases might indicate an intrinsic susceptibility to immune-mediated lung disease irrespective of asbestos exposure.

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Two malignant pleural mesotheliomas with unusual histological features. B. Goldstein. 1979;34(3):375-9. Case report PubMed · Publisher · Free full text

Abstract

Morphologically, mesotheliomas may be composed of epithelial and/or sarcomatous elements with various patterns, such as tubular, papillary, tubulopapillary, and diffuse epithelial or mixtures of these. Two cases are descirbed in which, in addition to typical mesothelioma, there was cartilage with foci of calcification and ossificated with the mesothelioma, which suggested that they formed an integral part of the tumour. One of the cases also showed a cuff of cartilage and bone round blood vessels and bronchioles in the lung parenchyma. The patholgenesis could be explained if the mesothelial cell is considered to be totipotent and able to give rise to epithelial and connective tissue elements. Other theories that must be considered are: that there are two separate neoplasms; that there is a circulating substance, perhaps induced by the mesothelioma, which stimulated the cartilage and bone formation; and that the cartilage and bone were due to a previous or associated infection such as tuberculosis. Calcification is also common in asbestotic pleural plaques.
An outbreak of pleural mesothelioma and chronic fibrosing pleurisy in the village of Karain/Urgüp in Anatolia. Y.I. Baris, A.A. Sahin, M. Ozesmi, et al. 1978;33(2):181-92. PubMed · Publisher · Free full text

Abstract

The 575 inhabitants of the remote Anatolian village of Karain suffered 11 deaths from pleural mesothelioma in 1975/76 and there were five cases of fibrosing pleurisy. In the previous five years there had been 25 cases of mesothelioma. Calcified pleural plaques were common on survey radiography. Asbestos does not occur in the local soil or rock, nor is it handled in the village, but a few fibres were found in the water. Fibres were also found in the pleural tissue of two of five cases examined. Inhabitants of the neighbouring villages are free of mesothelioma.
Malignant mesothelioma of the pleura in Barrow-in-Furness. J.R. Edge, S.L. Choudhury. 1978;33(1):26-30. PubMed · Publisher · Free full text

Abstract

Ffty cases of malignant pleural mesothelioma (47 men and 3 women) have been diagnosed during the period 1966-76 in Barrow-in-Furness, all of them histologically proved and accepted by the Pneumoconiosis Panel. At the time of writing only three survive. There was a history of industrial exposure to asbestos in all 47 men, who had worked in various trades in the shipyard, as had one of the women. One of the women was married to a shipyard plumber, who may have brought home asbestos dust on his clothes. Only one patient, a housewife, aged 28 at diagnosis, had no known asbestos contact. The asbestos content of the lungs has been measured in the last 20 cases, in 18 of whom it was found to be substantially greater than the accepted levels for the general population. In a small number studied by electron microscopy, the predominant fibre was crocidolite. A positive histological diagnosis was achieved in 39 subjects during life in the expectation of securing industrial compensation, but, in spite of this, less than half of the dependants are currently receiving payments. Metastases, though never clinically apparent, were frequent at necropsy.
Regional lung function in asbestos workers. D. Seaton. 1977;32(1):40-4. PubMed · Publisher · Free full text

Abstract

Regional lung function was measured using radioactive xenon-133 in a group of normal subjects and in two groups of asbestos workers. When compared with the normal group, patients with pulmonary asbestosis showed impaired ventilation of the lower zones. Subjects with calcified pleural plaques without radiological evidence of lung parenchymal fibrosis did not show this abnormality.
Relationship between occupations and asbestos-fibre content of the lungs in patients with pleural mesothelioma, lung cancer, and other diseases. F. Whitwell, J. Scott, M. Grimshaw. 1977;32(4):377-86. PubMed · Publisher · Free full text

Abstract

Whitwell, F., Scott, Jean, and Grimshaw, Myra (1977).Thorax, 32, 377-386. Relationship between occupations and asbestos-fibre content of the lungs in patients with pleural mesothelioma, lung cancer, and other diseases. The light-visible asbestos-fibre content of 300 lung specimens has been measured using a potash-digestion and phase-contrast microscopy technique, and the results have been correlated with the occupations of the patients. Among 100 pleural mesothelioma specimens were 88 where the patients had been exposed to asbestos, and in 73 of these (83%) the lung tissue contained over 100 000 asbestos fibres per gram of dried lung, and only one specimen showed less than 20 000 fibres per gram. When asbestosis was present, the lungs nearly always showed over 3 million fibres per gram. In 100 control lungs (those without industrial disease or lung cancer) there were less than 20 000 fibres per gram of dried lung in 71% of specimens. Lungs from 100 patients with lung cancer but no industrial disease contained less than 20 000 fibres per gram of dried lung in 80% of cases. Patients with parietal pleural plaques nearly all had over 20 000 fibres per gram in their lungs. The number of asbestos fibres found in the lungs was closely related to the occupations of the patients but not to their home environment. Patients who had lived near likely sources of atmospheric asbestos pollution did not have higher asbestos fibre counts than the rest of the patients. It is concluded that there is a definite dose relationship between asbestos exposure and mesothelioma formation but that' `sub-asbestosis' levels of asbestos exposure do not contribute to the formation of lung cancer in those not subjected to industrial asbestos exposure.
Electron microscopy in the cytological examination of metastatic pleural effusions. M. Legrand, R. Pariente. 1976;31(4):443-9. PubMed · Publisher · Free full text

Abstract

In a previous publication the ultrastructure of pleural effusions in cases of pleural mesothelioma was reported. The same method has now been applied to a study of effusions produced by pleural metastases. The findings are considered sufficiently conclusive to justify the use of electron microscopic cytology in determining the nature and sometimes the origin of such effusions.
Pleuropneumonectomy in the management of diffuse malignant mesothelioma of the pleura. Experience with 29 patients. E.G. Butchart, T. Ashcroft, W.C. Barnsley, et al. 1976;31(1):15-24. PubMed · Publisher · Free full text

Abstract

An analysis is made of the results of pleuropneumonectomy for diffuse malignant pleural mesothelioma in 29 patients and a comparison is made with the results of non-surgical treatment in a further 17 patients. A system of tumour staging is proposed, and the results are correlated with tumour stage and with histological type. Pleuropneumonectomy does not appear materially to affect the course of the disease in cases of mixed epithelial and mesenchymal histological type. However, stage I cases of pure epithelial histological type appear to carry a better prognosis, especially those whose histological structure consists entirely of abundant oedematous mucoid stroma with loosely arranged tumour cells. It is suggested therefore that only epithelial cases should be subjected to pleuropneumonectomy. Means of reducing operative mortality are discussed and alternative methods of treatment described.
Ultrastructural study of pleural fluid in mesothelioma. M. Legrand, R. Pariente. 1974;29(2):164-71. PubMed · Publisher · Free full text

Abstract

Legrand, M. and Pariente, R. (1974).Thorax, 29, 164-171. Ultrastructural study of pleural fluid in mesothelioma. By means of electron microscopy, three types of malignant cell can be identified in the pleural fluid of patients with pleural mesothelioma. These cell types are described, and the use of cytology in the differential diagnosis of pleural effusion is discussed.
Chest wall tumour following iodized talc pleurodesis. J.W. Jackson, M.H. Bennett. 1973;28(6):788-93. PubMed · Publisher · Free full text

Abstract

Jackson, J. W., and Bennett, M. H. (1973).Thorax, 28, 788-793. Chest wall tumour following iodized talc pleurodesis. A man of 37 had an iodized talc pleurodesis carried out for recurrent spontaneous pneumothorax. There was no history of industrial exposure to asbestos. Two years later he presented with pain in the right chest and radiographs at that time showed some localized pleural thickening at the site of the thoracoscopy cannulation for introduction of talc. A provisional diagnosis of talc granuloma, chemical abscess or tumour was made and exploratory thoracotomy revealed a tumour involving the chest wall, lung, and pleura which, on histological examination, showed adenocarcinoma of varying degrees of differentiation and in some parts also presenting a more squamoid appearance. Numerous doubly refractile talc particles were intimately associated with the tumour and fibrous tissue. Shortly after excision the patient developed evidence of systemic dissemination of the disease and died four months later. The possibility of this tumour being induced by the talc is discussed. A brief review is made of the various forms of talc used in surgery over the past 40 years and attention is drawn to the significance of the proportion of asbestos mineral which is present in talc as mined in various parts of the world. We do not consider that this is a case of mesothelioma of the pleura.
Electron microscopic studies in desquamative interstitial pneumonia associated with asbestos. B. Corrin, A.B. Price. 1972;27(3):324-31. PubMed · Publisher · Free full text

Abstract

A case of desquamative interstitial pneumonia (DIP) has been studied by electron microscopy in order to determine the nature of the alveolar cells. Those lining the alveolar walls proved to be granular pneumocytes (type II alveolar epithelial cells) while cells free in the lumen were alveolar macrophages. The brief literature describing the electron microscopic findings in DIP is reviewed. All workers agree that the lining cells are granular pneumocytes and most report a mixed free cell population with the emphasis shifting from desquamated epithelial cells to macrophages. In the present case asbestos bodies were also found in the lung, suggesting that DIP is not a specific disease entity.
Diffuse malignant pleural mesothelioma and asbestos exposure. F. Whitwell, R.M. Rawcliffe. 1971;26(1):6-22. PubMed · Publisher · Free full text

Abstract

Pleural mesothelioma has been diagnosed in 52 patients in three hospitals on Merseyside between 1955 and 1970, 60% being diagnosed from operation specimens and the rest from postmortem tissues. Necropsies eventually held on nearly half the operation cases confirmed the diagnosis, giving a necropsy rate of 70% for the series. The morbid anatomy conformed to earlier descriptions except that widespread metastases were much commoner than has usually been described. Histological findings agreed with previous accounts of the tumour, except that, in our hands, special acid mucopolysaccharide staining was less reliable than Southgate's mucicarmine, which was of value in differential diagnosis. Association with asbestos was confirmed from industrial histories in 80% of cases, the commonest industries involved being shipbuilding and repairing in men and sackware repairing in women. Lungs of industrial mesothelioma cases showed basal asbestosis in 17% and excessive asbestos bodies in almost all the rest. Quantitative comparison of asbestos bodies in lung smears from mesothelioma cases compared with lung smears from other Merseyside adults showed much higher counts in the mesothelioma cases. The interval from first exposure to asbestos until appearance of mesothelioma ranged between 13 and 63 years, with a mean of 42 years. We think the incidence of mesothelioma will continue to rise with the increased use of asbestos until about 40 years after adequate protective measures have been taken.
Aetiology of pleural plaques. V. Rous, J. Studený. 1970;25(3):270-84. PubMed · Publisher · Free full text

Abstract

Pleural plaques were found in 644 (6·6%) of 9,760 photofluorograms taken in 1965 in a region of Pelhřimov district; the incidence was highest in the age group 66-70 years. The advanced age of those affected may be explained by the greater frequency of the causative agent in the past. The disorder was known in Pelhřimov district as early as 1930; it was then thought to be posttuberculous. The past history of the cases was uninformative; as a rule, the only common previous disease was pleurisy with effusion, occurring in 9·7%. The general condition of those affected was excellent; only 8% were aware of the fact that pleural lesions were present. The disorder was found mainly in farmers, familial incidence was common, and if two generations of one family suffered from the condition, the older generation was affected in 100%. Pleural plaques consist morphologically of limited areas of hyalinized collagenous connective tissue with calcium salt deposits. Tubercle bacilli could not be cultivated from the lesions. Mineralological analysis showed no evidence of silicates in the pleural plaques and a normal content in the lungs. The aetiological factor responsible for the development of pleural plaques in Pelhřimov district is not known, but asbestos cannot be implicated. The unknown noxious agent is carried to the pleura by the lymph and blood stream. Pleural plaques are an endemic disorder. The traditional view that lesions are post-tuberculous appears, in the region submitted to this study, to be a possible explanation.

1960s

Cardiopulmonary function studies in workers dealing with asbestos and glasswool. J. Bjure, B. Soederholm, J. Widimsky. 1964;19(1):22-7. PubMed · Publisher · Free full text
Rheumatoid pneumoconiosis in association with asbestosis. W.K. Morgan. 1964;19(5):433-5. PubMed · Publisher · Free full text
The pathology of mesotheliomata and an analysis of their association with asbestos exposure. D.O. Hourihane. 1964;19(3):268-78. PubMed · Publisher · Free full text

Abstract

A study of the pathology of 34 cases of primary tumours (mesotheliomata) of the pleura and peritoneum shows these to be distinct and recognizable neoplasms which can be distinguished from primary carcinomata of the lung or other viscera. The association of these tumours with asbestos bodies in lung tissue is confirmed. Many of the cases gave no history of industrial exposure, and it is possible that temporary or relatively trivial exposure may have occurred. Once symptoms from the tumours have arisen, the prognosis appears to be measured in months rather than years.

PubMed has no abstract for this study. This is the authors' abstract, copied from the article.
Rheumatoid pneumoconiosis (Caplan's syndrome) in an asbestos worker. W.G. Tellesson. 1961;16(4):372-7. Case report PubMed · Publisher · Free full text

Abstract

A case of Caplan's syndrome in an asbestos worker is described. It differs from the first reported case of this association in the radiographic findings, namely, large cavitated nodules of unilateral distribution, in the absence of the classical features of pulmonary asbestosis, and in the late development of rheumatoid arthritis.

PubMed has no abstract for this study. This is the authors' abstract, copied from the article.
The pathology of asbestosis with reference to lung function. B.E. Heard, R. Williams. 1961;16(3):264-81. PubMed · Publisher · Free full text

1950s

Rheumatoid lung changes associated with asbestosis. A.G. Rickards, G.M. Barrett. 1958;13(3):185-93. PubMed · Publisher · Free full text
Massive pulmonary fibrosis from the inhalation of talc. A.C. Hunt. 1956;11(4):287-94. PubMed · Publisher · Free full text

1940s

The effect of asbestos, and of asbestos and aluminium, on the lungs of rabbits. E.J. King, J.W. Clegg, V.M. Rae. 1946;1(3):188-97. PubMed · Publisher · Free full text

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