Asbestos and the lung in the 21st century: an update

The asbestos‐related disorders (ARDs) are currently of significant occupational and public health concern. Asbestos usage has been banned in most developed countries, but asbestos is still used in many developing countries and the number of cases of ARDs worldwide is rising. Many countries are now experiencing an epidemic of ARDs that is the legacy of occupational exposure in the 1960s–1980s because of the long latency period between asbestos exposure and manifestation of disease. It is likely that asbestos‐related mortality and morbidity will continue to increase. Although the most feared complications of asbestos inhalation are the malignant conditions such as mesothelioma and lung cancer, asbestos inhalation more frequently results in benign conditions such as pleural plaques, diffuse pleural thickening, and asbestosis (pulmonary fibrosis due to asbestos exposure). Over recent years, there have been changes in the epidemiology of mesothelioma, in clinical management of ARDs and developments in new techniques for early detection of malignancy. This review provides an update on the respiratory manifestations of asbestos exposure and also considers advances in screening methods that may affect future management in the workplace.     

Asbestos-related disease

Inhalation of airborne asbestos fibres causes several diseases. These include asbestosis, lung cancer, malignant mesothelioma as well as pleural effusion, discrete (plaques) or diffuse benign pleural fibrosis and rolled atelectasis. The lag time between exposure and the development of disease may be many decades, thus the health risks of asbestos continue to be relevant despite bans on the use of asbestos and improvements in safety regulations for those who are still exposed. Asbestos was mined and used extensively in Australia for over 100 years and Australia is now experiencing part of a worldwide epidemic of asbestos-related disease. This review provides insight into the history and epidemiology of asbestos-related disease in Australia and discusses relevant clinical aspects in their diagnosis and management. The past and current medico-legal aspects of asbestos as well as currently evolving areas of research and future projections are summarized.     

Clinical aspects of malignant mesothelioma in Australia

Australia is currently experiencing an epidemic of malignant mesothelioma. The clinical aspects of malignant mesothelioma were investigated in 295 Australian patients as part of a national study of the disease. Most patients were male (91%), with the mean age at diagnosis being 64 years. The predominant cell type was epithelial (38%) and the majority of primary tumours arose from the pleura (94%). Mean survival was poor (17.6 months from first symptom; 11.8 months from diagnosis). Patients with a pleural primary tumour were more likely to present with dyspnoea, chest pain and cough; to have a pleural effusion diagnosed radiologically; and to have metastatic spread. Patients with a peritoneal primary tumour were more likely to present with weight loss, loss of appetite, abdominal pain and ascites; to have radiologic evidence of asbestos exposure; and to have spread along a needle track created during a diagnostic tap. A minority of patients had past thoracic conditions, or radiologic findings, specifically related to previous asbestos exposure. About one fifth of patients had no known asbestos exposure. Forty-one per cent of subjects received some form of chemotherapy, radiotherapy and/or surgery, but no formal disease staging had been documented for any patient. Proper controlled trials of secondary and tertiary treatments in malignant mesothelioma are now needed. (Aust NZ J Med 1993; 23: 19–25.)     

Epidemiology of pleural mesothelioma in a population with non-occupational asbestos exposure

Background and objective:   This study describes the epidemiology of malignant pleural mesothelioma (MPM) in a rural population with environmental asbestos exposure.
Methods:   Patients with diagnosed MPM were recruited and their relevant demographic and exposure data were analysed.
Results:   A total of 131 patients with MPM (59 men, 72 women) were studied. The patients' mean age was 57.8 years and the mean exposure duration was 28.9 years. The cumulative fibre count of the villagers ranged from 0.19 to 14.61 fibre/mL-years. Of the 131 patients, 85 had epithelial cell type, 20 had mixed, and eight had sarcomatous pleural mesothelioma. No significant relationship was found between asbestos fibre type and age, exposure period, or cellular type of MPM; similarly, no significant relationship could be found between the cellular type and age or exposure period. Patients with sarcomatous mesotheliomas were considerably older. Only five of 131 (3.8%) patients had a family history of mesothelioma.
Conclusions:   Environmental exposure to asbestos begins at birth and this may be important in the age of disease onset, if a threshold model for cancer initiation is operative. Both men and women had an excess risk of mesothelioma. Given that a family history of MPM was not common in this relatively homogenous patient group, a genetic predisposition to mesothelioma appears unlikely.     

Primary localized malignant biphasic mesothelioma of the liver in a patient with asbestosis

We report a case of primary localized malignant biphasic mesothelioma of the liver in a 66-year- old man associated with asbestosis. The tumor was detected as a hepatic nodule, 4 cm in diameter, in the right lobe （S8 segment） on CT scan. Histopathological examination demonstrated an intrahepatic tumor with central necrosis consisting of a papillary epithelioid pattern on the surface of the liver, microcystic （microglandular or adenomatoid） pattern mainly in the subcapsular area and sarcomatoid pattern intermingled with microcystic pattern in the major part of the hepatic nodular tumor. Tumor cells, especially of epithelioid type, showed distinct immunoreactivity for mesothelial markers （WT-1, calretinin, D2-40, CK5/6, mesothelin, thrombomodulin） and no immunoreactivity for epithelial （adenocarcinoma） markers （CEA, CD15, BerEP4, BG8, MOC31）. P53 immunoreactivity was detected focally in papillary epithelioid tumor cells and extensively in microcystic and sarcomatoid components, suggesting that the papillary epithelioid mesothelioma arose on the surface of the liver, and tumor cells showing microcystic and sarcomatoid patterns invaded and grew into the liver. To date, this is the first case of primary localized malignant biphasic mesothelioma of the liver, since all three primary hepatic mesotheliomas reported so far were epithelioid type.     

Observations on environmental asbestos exposure in a high risk area

Background and objective:   Environmental asbestos exposure is causally associated with various pulmonary pathologies. In Turkey, one of the most important sources of asbestos exposure is dust originating from the walls of homes whitewashed with white stucco. The main asbestos types implicated are tremolite and, to a lesser extent, chrysotile. This study investigated the presence and effect of environmental asbestos exposure in a small village in Isparta, Turkey.
Methods:   Samples of asbestos mine ore, whitewashed plaster from the interior walls of the houses and whitesoil from the outside walls of the houses were analysed. Chest radiographs of 132 villagers aged 30 years and over and living in the village during the study were obtained. Verbal histories from the relatives of people who had died from lung cancer or mesothelioma and hospital records contributed 13 cases to the study population, giving a total of 145 cases under study.
Results:   Chrysotile fibres were found in the old asbestos mine sample, and zeolite in the whitesoil sample from the outside walls. Abnormal CXR were found in 19 subjects (14. 4%), the most common being pleural calcifications and/or pleural plaques ( n  = 14, 10.6%). A further five subjects with pleural calcifications and/or pleural plaques were identified from verbal autopsy and hospital records. Malignant pleural mesothelioma was present in one living subject and four of the deaths. A possible familial clustering of lung cancer and malignant mesothelioma was noted.
Conclusion:   While tremolite asbestos is the asbestos found in most white soil in Turkey, in this village chrysotile asbestos was found in the white soil. Familial clustering may indicate genetic susceptibility or increased environmental exposure in some families.     

A case of malignant pleural mesothelioma following exposure to atomic radiation in Nagasaki

Abstract We report the case of a 75-year-old Japanese man who developed malignant mesothelioma in the left hemithorax 50 years after the dropping of the atomic bomb on Nagasaki in 1945. This may be the first reported case of malignant mesothelioma following exposure to atomic radiation. Asbestos is the leading cause of malignant mesothelioma, but radiation therapy is the primary non-asbestos-related cause. In the case of radiation therapy, the interval between exposure and the occurrence of malignant mesothelioma tends to be many years. This patient was at a high risk of malignant mesothelioma as he had been exposed to radiation from the atomic bomb and may also have had a history of asbestos exposure at the munitions factory where he was employed as a shipbuilder for 2 years. It has been suggested that combined exposure to atomic radiation and asbestos is associated with an increased incidence of malignant mesothelioma. If thickening of the pleura or pleural effusion is found in atomic bomb survivors, malignant mesothelioma should be considered as one of the options in the differential diagnosis, even although the atomic bomb attacks occurred several decades ago.     

Relative Leucopenia in the Peripheral Blood of Asbestos Miners: An Epidemiologic Analysis

The study examines differential leucocyte counts in blood of asbestos miners and quarriers identified during the course of a community health survey comprising 693 men over 25 years of age of all occupations. Subjects in the asbestos mining and quarrying occupational groups were present in the lowest total leucocyte quintile in significantly greater numbers than expected on the basis of an age-specific uniform leucocyte distribution based upon the total population of male workers. This relative leucopenia was not seen in their wives nor in any of the 22 other major occupational groups examined after their leucocyte counts were adjusted for age and sex variations.     

Diffuse Reflectance Infrared Fourier Transform Spectroscopy for the Determination of Asbestos Species in Bulk Building Materials

Diffuse reflectance infrared Fourier transform (DRIFT) spectroscopy is a well-known technique for thin film characterization. Since all asbestos species exhibit intense adsorptions peaks in the 4000–400 cm⁻¹ region of the infrared spectrum, a quantitative analysis of asbestos in bulk samples by DRIFT is possible. In this work, different quantitative analytical procedures have been used to quantify chrysotile content in bulk materials produced by building requalification: partial least squares (PLS) chemometrics, the Linear Calibration Curve Method (LCM) and the Method of Additions (MoA). Each method has its own pros and cons, but all give affordable results for material characterization: the amount of asbestos (around 10%, weight by weight) can be determined with precision and accuracy (errors less than 0.1).     

Association between increased small airway obstruction and asbestos exposure in patients with asbestosis

Background

Asbestos exposure may cause asbestos‐related lung diseases including asbestosis, pleural abnormalities and malignancies. The role of asbestos exposure in the development of small airway obstruction remains controversial. Anatomic and physiologic small airway abnormalities may develop as part of the pathophysiologic process of asbestosis. We hypothesized that inhalation of asbestos may induce small airway defects in addition to asbestosis and pleural abnormalities.

Methods

In total, 281 patients with newly diagnosed asbestosis were evaluated. Clinical data were collected from the patients' medical charts. The patients were classified into various stages according to their chest X‐ray findings using the International Labour Organization classification. Pulmonary function was evaluated by plethysmography and the forced oscillation technique.

Results

Expiratory flow, including the predicted values of the maximum expiratory flow between 25% and 50% of the forced vital capacity (MEF_25‐50), was significantly lower in the different stages of asbestosis. Accordingly, the predicted percentage of R₅–R₂₀ was significantly higher with increasing stages of asbestosis. Furthermore, the duration of exposure to asbestos was significantly associated with the forced expiratory volume in the first second (FEV₁)/forced vital capacity (FVC) ratio and the predicted percentage of MEF₂₅ or MEF₅₀ according to the regression analysis in non‐smoking patients with asbestosis. The predicted percentage of FEV₁ or the FEV₁/FVC ratio was significantly lower and the predicted percentage of R₅–R₂₀ was significantly higher in smokers than non‐smokers.

Conclusions

The patients with asbestosis have small airway obstructive defects that are significantly associated with asbestos exposure.     

Recent discovery of an old disease: malignant pleural mesothelioma in a village in south-east Turkey

BACKGROUND AND OBJECTIVE: Environmental asbestos exposure is reportedly common in some districts of Turkey. The aim of this study was to investigate the presence and effect of environmental asbestos exposure in a village in Gaziantep, Turkey, with reported cases of mesothelioma. METHODS: All villagers > or =14 years old were subject to an interview rediagnosis and a detailed questionnaire. Chest microfilms were performed in all cases, and additional standard CXRs were obtained when necessary. Samples collected from the natural mantle, and whitewash from the houses were analysed for the presence of asbestos. RESULTS: In total, 269 villagers took part in the study. The incidence of histopathologically diagnosed malignant pleural mesothelioma was 0.32% relative to the total village population in the year 2000. The verbal autopsy revealed eight possible cases of malignant pleural mesothelioma, all of whom had died within the past 12 years. Of these eight, there was a first-degree kinship between three, and additionally, these patients had a third-degree relationship with a biopsy proven case. Radiological evaluation showed pleural calcification and/or thickness in 3.3%, and pleural effusion in 0.4% of patients undergoing CXR. All houses in the village were constructed using adobe soil, and the interior whitewash was made from soil containing asbestos. Analysis of soil samples revealed tremolite and/or actinolyte asbestos. CONCLUSION: The current findings suggest that environmental asbestos exposure continue to be a serious health concern in the Gaziantep region of Turkey.     

Pleural mesothelioma: An approach to diagnostic problems

Abstract In the 1960s, a close relationship between heavy exposures to crocidolite asbestos and mesothelioma was established. The debate on the diagnosis of mesothelioma became complicated because of the possibility of litigation. Well differentiated mesothelioma cells are mucicarmine negative but alcian blue and periodic acid–Schiff (PAS) positive, which are removed by hyaluronidase and diastase digestion. By electron microscopy (EM), they show bush-like elongated, slender, and branching microvilli. By immunohistochemistry they express both keratin and vimentin but not carcinoembryonic antigenicity (CEA), B72.3, Ber–EP4, and Leu-M1. In poorly differentiated mesotheliomas, chromosomal and molecular biological alterations are common and complex but these alterations also overlap with that of poorly differentiated tumours of the lung and other organs. A poorly differentiated pleural tumour is most likely metastatic and needs good team work to locate the primary site. The diagnosis of a mesothelioma and asbestosis should be established separately. Future studies will be focused less on the phenotypic differences but more on the broad molecular and multi-phasic mechanisms of carcinogenesis, irrespective of the aetiological agents, in poorly differentiated tumours.     

Malignant mesothelioma

Malignant mesothelioma (MM) is an aggressive tumour that commonly affects the mesothelial surfaces of the pleural and peritoneal cavities, and occasionally, the tunica vaginalis and the pericardium. Formerly a rare tumour, MM is increasing in incidence in Australia due to the heavy nationwide use of asbestos from 1940 until the 1980s. The incidence is expected to peak in Australia in the next decade, mirroring the long latency period between asbestos exposure and development of MM. Diagnosis of MM can be difficult. Definitive pathological diagnosis is required and it often requires an experienced pathologist to differentiate MM from other benign or malignant processes. Treatment of MM requires a multidisciplinary approach, regardless of palliative or curative intent. Treatment options, such as surgery, chemotherapy, radiotherapy and active symptom control or a combination of these, may be used. Further research is needed to advance the therapeutic options for MM, and strategies to realize personalisation of therapy through discovery of predictive markers. In the Australian society where asbestos contamination of the built environment is very high, education and stringent public health measures are required to prevent a second wave of increased MM incidence.     

Asbestos ingestion and gastrointestinal cancer: a possible underestimated hazard

Introduction: The presence of asbestos fibres (AFs) in drinking water could be linked with gastrointestinal cancers. However, it is not regulated in several countries due to conflicting evidence.

Areas covered: Some reports mainly associated AF ingestion with gastric and colorectal cancer. Experimental evidence suggested a role for timing and extent of exposure, and showed that ingested AFs induce toxic effects on the stomach, ileum and colon, histological alterations and negative effects at a molecular level, cross the placenta and enter foetal organs (including the liver), and seem able to act as a co-carcinogen agent. Occupational studies suggest associations between asbestos exposure and intrahepatic cholangiocarcinoma, and observations exist indicating the possibility that AFs could enter the liver and bile through enteric absorption.

Expert commentary: A risk threshold (AF concentration in drinking water) for digestive cancers has not been convincingly identified so far and regulations, where adopted, have weak scientific basis and may not be adequate. With further and more definitive studies, evidence might become sufficient to justify monitoring plans, persuade countries with no current limits to set a maximum level of AFs in drinking water and might induce a revision of the existing legislations, pointing to efficient primary prevention policies.     

Hypertension and stroke in Asia: A comprehensive review from HOPE Asia

Stroke is the primary cause of disability and vascular death worldwide, including Asia. Asian characteristics that differ from the West lead to higher stroke incidence. Stroke epidemiology studies in Asia have shown varying levels of mortality, incidence, prevalence, and burden of disease. Hypertension is the most prevalent risk factor found in Asia. Besides ethnicity that is associated with stroke incidence, both systolic blood pressure, diastolic blood pressure, and blood pressure variability are positively correlated with stroke incidence. Post‐stroke cognitive impairment is one of the sequelae that affect one‐third of stroke survivors and has become a significant public health concern that is often neglected despite its increasing prevalence. Therefore, it is very important to prevent recurrence by treating stroke optimally and effectively. Increasing awareness and treatment adherence to hypertension, the leading risk factor for stroke, became the main goal in several countries in Asia.