P. De Vuyst

Guidelines of the European Respiratory Society and the European Society of Thoracic Surgeons for the management of malignant pleural mesothelioma

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

Guidelines for mineral fibre analyses in biological samples: report of the ERS Working Group

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

Asbestosis, pleural plaques and diffuse pleural thickening: three distinct benign responses to asbestos exposure

The aim of this study was to investigate by computed tomography (CT) whether asbestosis, diffuse pleural thickening and/or pleural plaques are statistically associated. We also tried to find criteria to differentiate between diffuse and circumscribed pleural thickening. From 231 exposed workers, only those subjects whose radiograph showed neither bilateral calcified pleural plaques nor small pulmonary opacities higher than 1/1 grade according to the 1980 International Labour Office (ILO) Classification were considered. Scans were assessed for the presence of subpleural curvilinear lines, septal and intralobular lines, parenchymal bands, honeycombing, rounded atelectasis, pleural plaques and diffuse pleural thickening. CT scans revealed pleural and/or lung abnormalities in 99 workers. Pleural plaques were unilateral in one-third of cases with plaques. Diffuse pleural thickening, parenchymal bands and rounded atelectasis were unilateral in, respectively, 62 and 69 and 75% of cases with the abnormality. Septal and intralobular lines, and honeycombing were always bilateral. CT signs could be grouped into three patterns: 1) septal and intralobular lines, and honeycombing corresponding to pulmonary fibrosis; 2) pleural plaques corresponding to parietal pleural fibrosis; and 3) diffuse pleural thickening, rounded atelectasis and parenchymal bands corresponding to visceral pleural fibrosis. In these workers with a normal or near-normal radiograph, three groups of subjects with different responses were distinguished. Crows feet and rounded atelectasis help to differentiate plaques from diffuse thickening.

Acute and long term respiratory damage following inhalation of ammonia.

A lifelong non-smoker who was the victim of a massive accidental exposure to anhydrous ammonia gas was followed up for 10 years. In the acute phase the patient presented with severe tracheobronchitis and respiratory failure, caused by very severe burns of the respiratory mucosa. After some improvement he was left with severe and fixed airways obstruction. Isotope studies of mucociliary clearance, computed tomography, and bronchography showed mild bronchiectasis. It is concluded that acute exposure to high concentrations of ammonia may lead to acute respiratory injury but also to long term impairment of respiratory function.

Respiratory health effects of man-made vitreous (mineral) fibres

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

Conventional and high-resolution CT in asymptomatic asbestos-exposed workers.

To compare the value of conventional CT (CCT) and high-resolution CT (HRCT) to detect benign asbestos-related diseases, 159 exposed workers with a normal chest radiography were imaged by both techniques. Pleural plaques were detected in a total of 59 cases (37.1%). Ten cases (16.9%) were detected by CCT only and one case (1.7%) by HRCT only. Pulmonary lesions compatible with parenchymal asbestosis were detected by HRCT in 20 cases, whereas CCT showed abnormalities in 45% of these. Rounded atelectasis was equally recognized by both techniques. The results confirm that in a subject with a normal chest radiography, HRCT is a better diagnostic tool to demonstrate lesions of asbestosis. On the other hand, HRCT is insufficient to exclude the presence of pleural plaques. When HRCT does not reveal pleural abnormalities, CCT should be performed.

Micronodules and emphysema in coal mine dust or silica exposure: relation with lung function

The aim of this study was to investigate the respective effects of micronodules and pulmonary emphysema, detected by computed tomography (CT), on lung function in workers exposed to silica and coal mine dust. Eighty-three subjects exposed to silica (n=35) or to coal mine dust (n=48), without progressive massive fibrosis, were investigated by high-resolution and conventional CT scans to detect micronodules and to quantify pulmonary emphysema by measuring the relative area of the lung with attenuation values lower than -950 Hounsfield units. Sixty-six (54.5%) subjects had evidence of micronodules on CT scans. Smokers had micronodules more rarely than nonsmokers. Significant correlations were found between the forced expiratory volume in one second (FEV(1); % predicted) (r=-0.41, p<0.001), FEV1/vital capacity (VC) (r=-0.61, p<0.001), diffusing capacity of the lung for carbon monoxide (DL,CO) (r=-0.36, p<0.001) and the extent of emphysema. No difference was demonstrated in the linear relationships between the extent of emphysema and the pulmonary function according to the type of exposure or the presence of micronodules on CT scans. This study suggests that micronodules detected by computed tomography have no influence, by themselves, on pulmonary function and that they should only be considered as a marker of exposure.

Erionite bodies and fibres in bronchoalveolar lavage fluid (BALF) of residents from Tuzkoy, Cappadocia, Turkey.

OBJECTIVES The high incidence of malignant mesothelioma in some villages of Cappadocia (Turkey) is due to environmental exposure to erionite fibres. The aim was to evaluate the fibre burden in bronchoalveolar lavage fluid (BALF) from inhabitants of an erionite village and compare it with Turkish subjects with or without environmental exposure to tremolite asbestos. METHODS Ferruginous bodies (FBs) and fibres were measured and analyzed by light and transmission electron microscopy (TEM) in the BALF of 16 subjects originating from Tuzköy. RESULTS FBs were detected in the BALF of 12 subjects, with concentrations above 1 FB/ml in seven of them. Erionite was the central fibre of 95.7% of FBs. Erionite fibres were found in the BALF of all subjects, by TEM, and these fibres were low in Mg, K, and Ca compared with erionite from Tuzköy soil. The mean concentration of erionite fibres in BALF was similar to that of tremolite fibres in Turks with environmental exposure to tremolite. The proportion of fibres longer than 8 μm in BALF represented 35.6% for erionite compared with 14.0% for tremolite. The asbestos fibre concentrations in erionite villagers was not different from that in Turks without environmental exposure to tremolite. CONCLUSION Analysis of BALF gives information about fibre retention in populations environmentally exposed to erionite for whom data on fibre burden from lung tissue samples are scarce. This may apply to exposed Turks having emigrated to other countries.

Asbestos bodies in bronchoalveolar lavage fluids of brake lining and asbestos cement workers.

Asbestos body (AB) concentrations in bronchoalveolar lavage samples of 15 brake lining (BL) workers exposed only to chrysotile have been determined and compared with those from 44 asbestos cement (AC) workers extensively exposed to amphiboles. The mean AB concentrations (263 +/- 802 and 842 +/- 2086 AB/ml respectively) for those groups did not differ significantly but were much higher than those found in control groups. Analytical electron microscopy of asbestos body cores showed that in the BL group 95.6% were chrysotile fibres whereas in the AC group amphiboles accounted for 93.1%. The size characteristics of the central fibres differed for chrysotile and amphibole AB, the former being shorter and thinner. Examination of repeated bronchoalveolar lavage samples showed that the mechanisms of clearance of chrysotile fibres do not affect AB concentration for at least 10 months after cessation of exposure. It thus appears that routine counting of ABs in BAL allows the assessment of current or recent occupational exposures to asbestos. Exposures to chrysotile lead to AB concentrations comparable with those encountered in exposures to amphiboles.

Macroscopic assessment of pulmonary emphysema by image analysis.

AIMS--To propose a computerised image analysis based method for measuring, on paper mounted lung sections, the area macroscopically occupied by emphysema. METHODS--The study was based on the assessment of 69 lung sections prepared following a modified Gough-Wentworth technique. The results obtained from image analysis, point counting, and panel grading methods were compared, as was the repeatability of image analysis and panel grading. RESULTS--The results from image analysis and from point counting were not significantly different (p = 0.609) and significant quadratic regressions (r = 0.96, p < 0.001) were found between measurements from image analysis and from panel grading, the computerised technique being shown to be the most reproducible. CONCLUSIONS--Image analysis is a valuable and reproducible method to measure the area of lung macroscopically involved by emphysema.