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 approximately 10% of cases. Therefore, we propose using specific immunohistochemistry markers on pleural biopsies. In the absence of a uniform, robust and validated staging system, we advice use of the most recent TNM based classification, and propose a three step pre-treatment assessment. Patient's performance status and histological subtype are currently the only prognostic factors of clinical importance in the management of MPM. Other potential parameters should be recorded at baseline and reported in clinical trials. MPM exhibits a high resistance to chemotherapy and only a few patients are candidates for radical surgery. New therapies and strategies have been reviewed. Because of limited data on the best combination treatment, we emphasise that patients who are considered candidates for a multimodal approach should be included in a prospective trial at a specialised centre.

[The missions of the Occupational Diseases Fund. Under-claim and recognition of occupational lung cancer, in particular those related to asbestos]. / Les missions du Fonds des Maladies Professionnelles. La sous-déclaration des cancers respiratoires professionnels, en particulier dus a l'amiante.

The missions of the Occupational Diseases Fund are defined in application of the law regarding the insurance against occupational diseases. The workers covered by this law are granted several rights, such as a financial compensation in case of temporary or permanent disability, a further compensation if they have to be taken away from the risk in the workplace, the reimbursement of health care costs related to the occupational disease, or the payment of an annuity to the widow(er) if death is its ultimate consequence. Among the compensable diseases, we shall focus on lung cancer, and especially the one related to asbestos exposure. This type of cancer is clearly under-registrated in Belgium as in most countries of the European Union, leading to an insufficient number of cases entitled to compensation by our institution. In this instance, the insurance against occupational diseases and all related social advantages are hugely under-exploited in our country. It is our duty to increase doctors' awareness of the problem and spread accurate information to reverse this trend and provide occupational cancer cases with a legitimate compensation, in particular those related to asbestos. A wider knowledge of the occupational history of cancer patients, thanks to occupational physicians, and a better use of mineralogical analyses on lung samples, would improve this situation inacceptable on any level : medical, social or even human.

Pneumoconiosis after sericite inhalation.

BACKGROUND: Between 1997 and 1999 three sericite plant workers in Parana, Brazil, were diagnosed with pneumoconiosis. AIMS: To investigate and describe the radiological, clinical, and pathological changes in miners and millers exposed to sericite dust with mineralogical characteristics of inhaled dust. METHODS: The working premises were visited to examine the sericite processing and to classify the jobs according to make qualitative evaluation. Respirable dust was collected and the amount of crystalline silica and particle size distribution were measured. Forty four workers were examined by a standard questionnaire for respiratory symptoms, spirometry, and chest x ray. Material from an open lung biopsy was reviewed for histopathological and mineralogical analysis, together with sericite samples from the work site to compare the mineral characteristics in lung lesions and work area. RESULTS: Respirable dust contained 4.5-10.0% crystalline silica. Particle size distribution showed a heavy burden of very fine particles (23-55%) with a mean diameter of <0.5 microm. Mean age of sericite miners was 41.0 (11.9) and mean number of years of exposure was 13.5 (10.1). In 52.3% of workers (23/44), chest radiographs presented a median category of 1/0 or above, and 18.2% (8/44) had a reduced FEV1. There was a significant association between exposure indices and x ray category. Histological studies of the lung biopsy showed lesions compatible with mixed dust fibrosis with no silicotic nodules. x Ray diffraction analysis of the lung dust residue and the bulk samples collected from work area showed similar mineralogical characteristics. Muscovite and kaolinite were the major mineral particle inclusions in the lung. CONCLUSION: Exposure to fine sericite particles is associated with the development of functional and radiological changes in workers inducing mixed dust lesions, which are distinct histologically from silicosis.

Biopersistence of respirable synthetic fibers and minerals: point of view of the chest physician.

Problems of diagnosis related to the presence or absence of particles in lung and pleural tissues are discussed from the clinician's viewpoint. The advantage of applying mineralogical analytical techniques is considered.

Comparative analysis of inhaled particles contained in human bronchoalveolar lavage fluids, lung parenchyma and lymph nodes.

Translocation of inhaled particles from the alveolar spaces to lung parenchyma and lymph nodes is one of the mechanisms that determine the biopersistence of particles. This study compares the nonfibrous particulate burden in bronchoalveolar lavage (BAL) fluids, lung parenchyma, and thoracic lymph nodes and attempts to detect the degree of differentiation, if any, based on particle size or type. This comparison can only be done on BAL, lung parenchyma, and lymph node samples collected from the same subject over a short time. Patients undergoing surgical lung resection are suitable for this purpose. Particles recovered by digestion-filtration were counted, sized, and analyzed by analytical transmission electron microscopy. Total particle load ranges grossly between 10(5) to 10(7) p/ml in BAL, 10(9) to 10(10) p/g dry tissue in parenchyma and 10(10) to 10(11) p/g dry tissue in lymph nodes. Diameters are log-normally distributed and mean diameters range between 0.5 to 0.9 micron. Nonlamellar silicate particles have a significantly larger diameter in lymph nodes. Differences in particle type between the three sampling sites are small and nonsystematic.

High-altitude pulmonary edema with primary pulmonary hypertension.

A 43-year-old woman had two episodes of lung edema at moderate altitudes. She had taken slimming pills containing fenfluramine hydrochloride and diethylpropion hydrochloride. At sea level, catheterization of the right side of the heart showed a mean pulmonary artery pressure of 16 mm Hg, which increased to 34 mm Hg with mild exercise in a supine position. An extensive workup failed to identify a cardiac or a pulmonary cause of pulmonary hypertension. This patient experienced mild primary pulmonary hypertension related to the intake of anorexigens, which was revealed by high-altitude pulmonary edema.

Bloody pleural effusion in a patient with sarcoidosis.

A 50-year old man was evaluated for pleuritic pain.. Chest roentgenogram showed diffuse parenchymal infiltrates and bilateral effusion that, on thoracocentesis, was found to be a bloody fluid. Biopsy of paratracheal nodes demonstrated abundant noncaseating granulomas consistent with sarcoidosis. Prednisone therapy resulted in rapid disappearance of the pleural effusion, progressive clearing of parenchymal infiltrates, and marked improvement of pulmonary function tests. Sarcoidosis should be included in the differential diagnosis of bloody pleural effusion.

Wegener's granulomatosis presenting as acute respiratory failure with anti-neutrophil-cytoplasm antibodies.

Anti-neutrophil-cytoplasm antibodies recently have been reported as serologic markers of Wegener's granulomatosis. We describe two cases in which this test appeared to be of great value in the diagnosis of Wegener's granulomatosis presenting as acute respiratory failure, a clinical setting in which it may be the only diagnostic test that can be safely and easily performed.

Environmental asbestosis complicated by lung cancer.

Diagnosis of asbestosis and bronchiolo-alveolar carcinoma was made in a 55-year-old Turkish woman who was a nonsmoker. She originated from and was living in an area with a high prevalence of environmental diseases attributed to tremolite asbestos. Mineralogic analysis of lung tissue revealed very high concentrations of asbestos bodies (1.64 x 10(6)/g of dry tissue) and tremolite fibers (173.7 x 10(6) of dry tissue). This case illustrates the following points: (1) In some areas, environmental exposure can lead to cumulated fiber retention comparable to occupational exposure and thus can represent a risk for lung fibrosis (asbestosis). (2) Lung cancer as a complication of environmental asbestosis also should be considered as a potential environmental disease.

Pneumonitis complicating low-dose methotrexate therapy for rheumatoid arthritis. Discrepancies between lung biopsy and bronchoalveolar lavage findings.

Two very similar cases of drug-induced pneumonitis complicating treatment of rheumatoid arthritis with low-dose methotrexate are presented. Diagnosis was suggested by clinical history and findings, but the bronchoalveolar lavage showed a high percentage of neutrophils, an unusual feature in methotrexate-induced pneumonitis. Transbronchial lung biopsies (TBB) confirmed the diagnosis by showing interstitial lymphocytic infiltrate with microgranulomas. Although histologic findings are not strictly pathognomonic, when a differential diagnosis has to be made with infectious and rheumatoid lung disease, TBB appears to be of great promise.

Whole lung sections for computed tomographic-pathologic correlations. Modified Gough-Wentworth technique.

RATIONALE AND OBJECTIVES: High-resolution computed tomography of the lung has been advocated in the evaluation of interstitial lung diseases and emphysema. To provide material for correlations with gross pathology and macroscopic quantitation of emphysema, the authors have shortened and simplified the Gough-Wentworth technique. METHODS: The method permits more precise correlation of cross-sectional images and pathologic specimens and is less time-consuming. RESULTS AND CONCLUSIONS: This modified method can be routinely performed in a clinical laboratory of pathology and provides paper-mounted whole lung sections within four days. The sections are protected by a transparency film.

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.

Assessment of asthma severity and treatment by GPs in Belgium: an Asthma Drug Utilization Research Study (ADUR).

A prospective study was performed between June 1996 and December 1997, to identify how general practitioners (GPs) in Belgium assess asthma severity and how they treat asthma according to their severity assessment. Three hundred and sixty-five GPs included 1376 already diagnosed and treated asthmatics. The GPs used a questionnaire providing data on patient demographics, aetiology of asthma, symptoms and medication use. The patients provided a complete diary card of day and night symptoms and morning and evening peak expiratory flow rates during a 3-week period. Asthma severity as assessed by GPs was compared with the severity according to the GINA guidelines. Along the same line, asthma treatment was evaluated according to the GPs assessment of severity and according to the GINA guidelines. Confronting the assessment of asthma severity by the GPs with the GINA criteria revealed that about 20% and 2% of the patients' asthma severity respectively were under- and over-estimated, respectively (using a discrepancy between GPs and GINA assessment of severity by 2 or more classes). Using the GINA criteria for treatment, only 37.5% of the patients seemed to be correctly treated. Taking a discrepancy between GINA assessment and treatment of two classes as an error, 2.3% and 23.4% of the asthmatics are over- and under-treated, respectively. In conclusion, this study provides evidence that GINA guidelines seem not to be adequately interpreted and implemented by GPs in Belgium. Improvement of the assessment of asthma severity is definitely needed and may lead to more appropriate use of asthma medication.

Concentration of tobramycin given by aerosol in the fluid obtained by bronchoalveolar lavage.

Whereas previous studies have used only bronchial secretions and sputum, in the present study, bronchoalveolar (BAL) fluid was analysed for tobramycin levels after aerosolization of this antibiotic. In 20 adult patients with a variety of lung disorders, the concentration of tobramycin obtained in the first aliquot of the bronchoalveolar fluid varied from less than 0.1 to 9.2 micrograms ml-1 (mean 2 +/- 2.26 micrograms ml-1) with 18 samples above 0.4 micrograms ml-1. In most of the cases, the concentration of tobramycin achieved values of tobramycin in excess of the minimal inhibitory concentration for most of the microorganisms. Thus, sampling fluids by the bronchoalveolar technique offers a suitable method to study antibiotic levels at the site of broncho-pulmonary infection. These results may help explain why aerosol antibiotic treatment appears to be useful in selected patients, especially in cystic fibrosis patients chronically infected with Pseudomonas aeruginosa.

[Respiratory toxicity due to atmospheric pollutants. General review and a study of the relation to respiratory infections]. / Toxicité respiratoire des polluants atmosphériques. Revue générale et étude de la relation avec les infections respiratoires.

The main primary pollutants released into the atmosphere are sulfur dioxide (SO2), nitrogen monoxide and dioxide (NOx), particulate dust and in a less important part carbon monoxide (CO), hydrocarbons and heavy metals (Pb, Cd). Sulfur and nitrogen oxides are released from combustion of coals and fuels. Sulfates, nitrates and ozone are secondary pollutants resulting from chemical reactions within the atmosphere. While governmental directives limiting emissions have decreased SO2 and particulate matter levels, air quality in urban regions has improved in the last two decades. The role of air pollution as a risk factor for respiratory infections is difficult to address. Animal experiments demonstrate that air pollutants decrease the efficacy of lung defense mechanisms and increase the sensibility to respiratory infections. Nevertheless, because of difference in sensitivity between animal species and between exposure conditions, these effects are difficult to extrapolate to humans. Moreover, it is obvious that direct exposure studies of the sensibility of humans to respiratory infections are rare for ethical reasons. Epidemiological data addressing the role of air pollutants at usual levels can only suggest that some pollutants (SO2, suspended particulates) constitute a risk factor for respiratory infections. Since most of these studies do not include bacteriologic and virologic confirmation, it is unclear whether this respiratory morbidity is due to respiratory irritation or infection. In conclusion, we think that high concentrations of air pollutants are very likely to increase sensibility to respiratory infections in humans. There are however no sufficient data to clearly establish whether air pollution constitutes a risk factor for respiratory infections at usual ambient concentrations.

[Broncho-alveolar lavage. From technical aspects to standards of interpretation]. / Le lavage broncho-alvéolaire. Des aspects techniques aux règles d'interprétation.

Broncho-alveolar lavage is a simple investigation to carry out and enables the gathering of biological information such as inflammatory and immuno-competent cells, tumour cells, microorganisms as well as mineral particles which are found in the biological milieux present in the distal air spaces. The performance of LBA assumes a mastering of the correct technical aspects of this method of investigation, particularly in the phase of injecting and recovering of physiological saline and an understanding of the indications and contraindications of the technique. The interpretation of the information gathered by cytological, microbiological, mineralogical and biochemical study of the bronchoalveolar lavage liquid should comply with a strict set of rules and justifies a close working contact between the clinician and the biological scientist.

[Alveolar proteinosis in a facade plasterer. A sequential study of bronchoalveolar lavage and thoracic computerized tomography]. / Protéinose alvéolaire chez un ravaleur de façade. Etude séquentielle du lavage broncho-alvéolaire et de la tomodensitométrie thoracique.

Alveolar proteinosis is a rare disease. We report a case occurring in a patient who smoked and was a facade plasterer who was treated with repeated pulmonary lavage. A mineral analysis of the lavage fluid recovered a significant amount of silica and iron oxide confirming the massive exposure of the patient to these minerals. The favourable outcome over the next 7 years was associated as regards respiratory function, with a progressive improvement in lung volumes and pulmonary output and of CO diffusion capacity, as regards broncho-alveolar lavage there was a regular increase in the cellularity and finally as regards CT scanning (at high resolution) there was a progressive clearing of the alveolar opacities only leaving the persistent opacities in the interstitium.

[The diagnostic value of asbestos bodies in mesotheliomas]. / Intérêt diagnostique des corps asbestosiques dans le mésothéliome.

The exposure of asbestos was studied in 31 cases of mesothelioma from case histories and by microscopic mineralogical analysis of the broncho-alveolar lavage fluid (BAL) (31 cases) and of pulmonary tissue (5 cases). When definite exposure had occurred the lavage contained asbestos bodies in every case, except one patient with severe airflow obstruction. The most positive lavages, probably reflecting exposure to industrial amphiboles, were found in patients presenting with radiological evidence of asbestosis. Two patients had positive lavages 50 years after exposure had ceased. The lavage confirmed exposure in 6 out of 11 suspected cases and revealed contamination by asbestos in a further 4 cases, in a group of 6 not known to have been exposed. In 19.3% of cases there was a low concentration of asbestos bodies (less than 1AB/ml of BAL), comparable to what is found in 16.2% of controls from an urban population. An analysis of lung tissue confirmed massive exposure (greater than 20 000 AB/g) in two cases and in particular revealed a significant dust load (greater than 250 AB/g) in patients presenting with a weak positive BAL. Thus it seems that all the positive results should be taken into account. Of the 31 cases, 8 had a BAL without asbestos bodies. These were either mesotheliomas not linked to the inhalation of asbestos, or were the result of false negatives on account of artefacts related either to the BAL technique itself or linked to the technique of mineral analysis. Indeed the microscopic counts of asbestos bodies probably underestimate certain exposures, notably environmental exposure to chrysotile.

[Environmental mesotheliomas in northeast Corsica]. / Les mésothéliomes environnementaux en Corse du nord-est.

Since 1980, we have collected fourteen cases of mesothelioma induced by environmental exposure to asbestos, going back to childhood in patients from north-east Corsica, in a region which was remote from the asbestos mine of Canari. There were eight men and six women with a mean age of 69.5 +/- 4 years. Six patients presented with bilateral calcified pleural plaques as evidence of environmental exposure. The mineral analysis carried out on five patients (four had thoracoscopies and one an alveolar lavage), showed a moderate deposit of chrysotile (0.3 to 3.4 x 10(6) fibres per gram of dry tissue), and elevated level of tremolite (1.4 to 62 x 10(6) fibres/g). The ambient dosage of asbestos has confirmed the existence of environmental pollution by chrysotile fibres and above all by tremolite. In addition, the same type of fibres have been identified in the parietal pleural of animals subjected to the same risk. In this region, the risk is estimated, on the basis of our results, as 10 cases of mesothelioma per 100,000 inhabitants per year.

[Asbestos: current knowledge and perspectives]. / Amiante: constats et perspectives.

Diseases due to asbestos inhalation are not only a concern for occupational physicians, but also for general practicioners and pneumologists. The real or supposed risk has extended beyond the factories employing "primary asbestos workers" to thousands of people exposed to this material or simply working in buildings insulated with asbestos. The spectrum of asbestos-related diseases has changed: asbestosis (parenchymal fibrosis due to asbestos) tends to disappear, whereas the incidence of pleural lesions, which can be associated with lower cumulative exposures, increases. Patients with asbestos related diseases do not die any more from respiratory failure but from late neoplastic complications, such as mesothelioma and lung cancer. The lack of interest and of training in occupational medicine leads to an underrecognition and an underestimation of cancers due to asbestos by the physicians. Recent progresses in CT imaging and evaluations of exposure to fibers through mineralogical analysis of lung samples have led to improve the diagnostic approach of fiber-related diseases.