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The epidemic of asbestos-related diseases in New Zealand.

New Zealand is a small country with a big asbestos disease problem. The lack of action on warnings in the 1960s and 1970s has led to epidemics of mesothelioma and asbestosis, which can be clearly documented via the death and cancer registers. In addition, an uncertain number of lung cancers due to asbestos exposure has occurred. The epidemic started in the 1980s, and will eventually have cost the lives of at least 2000 to 3000 workers. Prevention against ongoing exposures from asbestos installed in buildings is essential, and another key issue for New Zealand is to ensure that fair workers' compensation is provided to all victims of asbestos diseases.

Asbestosis↗

Asbestos in the sputum, crackles in the lungs, and radiologic changes in women exposed to asbestos.

In a rural community in South Africa historically exposed to asbestos environmentally and occupationally, 200 women who had worked with asbestos and applied for medical examination to determine compensable asbestos disease were evaluated. Clinical and radiologic evaluation, sputum collection, and microscopic analysis were done. A questionnaire elicited type of exposure, duration, decade of first work exposure, and environmental exposure. Crackles were present in the lungs of 166 women and asbestos fibers and ferruginous bodies were present in 122. Asbestosis was identified in 26 and plural plaques in 62. Auscultation for crackles (rales) is useful in the initial examination of former asbestos workers in rural communities of developing countries.

Age Distribution↗

Can semi-automated image cytometry on induced sputum become a screening tool for lung cancer? Evaluation of quantitative semi-automated sputum cytometry on radon- and uranium-exposed workers.

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

Adult↗

The role of environmental and occupational exposures in Turkish immigrants with fibre-related disease.

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

Adult↗

Trends in asbestos body counts in bronchoalveolar lavage fluid over two decades.

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

Asbestos↗

Oxidized BAL fluid proteins in patients with interstitial lung diseases.

Oxygen-derived free radicals, released by phagocytic cells, have been postulated to contribute to lung tissue damage. We therefore investigated oxidative damage to proteins from bronchoalveolar lavage fluid (BALF) as an indicator of oxidative stress and to assess antioxidant defences in the lungs. We examined BAL fluids from patients with interstitial lung diseases, such as idiopathic pulmonary fibrosis (IPF, nonsmokers (NS) and smokers (S)), sarcoidosis (SARC, nonsmokers), and asbestosis (ASB, ex-smokers (EXS)). The oxidation of BALF proteins is accompanied by the introduction of carbonyl groups into their amino acid side-chains and can be quantitated by labeling these groups with tritiated borohydride. The total lung content of oxidized proteins recovered by bronchoalveolar lavage (BAL) was 0.3 +/- 0.07 nmol carbonyl.mL-1 BALF (mean +/- SEM) in the NS control group (n = 9) and tended to be increased, in the asymptomatic S group (n = 8; 0.59 +/- 0.14 nmol.mL-1). This parameter was significantly elevated both in IPF-NS (n = 14; 0.84 +/- 0.2 nmol carbonyl.mL-1 BALF) and SARC-NS (n = 15; 0.73 +/- 0.16 nmol.mL-1) as compared with the NS control. On the contrary, in smoking patients with IPF (n = 6; 0.41 +/- 0.1 nmol carbonyl.mL-1 BALF) and also in ASB-EXS (n = 6; 0.37 +/- 0.06 nmol.mL-1) it was not different from NS controls. The total amount of oxidized proteins correlated positively with the absolute number of eosinophils (EOS) in IPF-NS, IPF-S and SARC, and also with absolute polymorphonuclear neutrophil (PMN) numbers in IPF-NS and IPF-S. In conclusion, oxidative damage of BALF proteins occurred in nonsmoking patients with IPF and SARC. The amount of oxidized bronchoalveolar lavage fluid protein may provide a quantitative assessment of oxygen burden, a balance between oxidant stress and antioxidant defences.

Adult↗

Asbestos bodies and fibers in lung tissues.

It is suggested that the ratio of asbestos bodies observable by light microscopy to asbestos fibers counted by electron microscopy be examined in a series of cases of asbestosis of varying severity. If the ratio is reasonably constant an estimate of fiber content could be made from the more easily conducted count of asbestos bodies by light microscopy.

Asbestos↗

Correlation between the tissue response and asbestos fiber content.

Asbestos fiber concentration increases in proportion to the degree of pulmonary fibrosis as far as the moderate grade. No such correlation occurs with severe asbestosis, nor with the morphological form which the fibrosis assumes, and here secondary factors may be concerned. Electron microscopy suggests that optically visible fibers constitute a reasonably constant proportion of the total irrespective of the pathological reaction. Light microscopy may thus afford a guide to the total asbestos concentration. Finally, the development of mesothelioma, whether of the pleura or the peritoneum, appears to be unrelated to the concentration of coated or uncoated asbestos fibers residing in the lung.

Asbestos↗

Effect of asbestos on the metabolism of vasoactive substances in isolated perfused guinea pig lungs.

The measurement of pulmonary metabolism of three vasoactive substances and quantitative assessment of changes in lung morphology were performed in a long-term study of asbestos-exposed guinea pigs. Animals received intratracheal injections of a single dose of a sterile suspension of Canadian chrysotile B (5 mg), while control animals received only saline. Six months after the treatment, the guinea pigs were sacrificed, the lungs removed, perfused via the pulmonary artery and the metabolism of vasoactive substances was assessed (in vitro) in a cascade superfusion system. At the end of the experiments, the lungs were fixed in a glutaraldehyde solution for microscopic examination. The tissue response consisted of both inflammatory reaction of terminal and respiratory bronchioles and diffuse alveolar septal infiltration with interstitial fibrosis. The reaction was characterized at six months by a progressive bronchiolitis obliterans with fibroblastic proliferation and collagen formation. The development of the disease did not cause significant changes in the metabolism of acetylcholine and bradykinin. However, the metabolism of prostaglandin E2 decreased with the appearance of the bronchiolitis obliterans. Our results showed that asbestos exposure may produce early biochemical changes resulting in altered lung metabolism of vasoactive substances; these modifications could contribute to the pathogenesis of asbestosis.

Acetylcholine↗

Historical developments and perspectives in inorganic fiber toxicity in man.

The first patient known to have died from asbestosis (1900) began work in 1885, approximately 5 years after the industrial use of asbestos began in Britain. Mineral particles were found in his lungs. No special comment was made of their fibrous nature then nor when the first case was reported in 1924. The various neoplasms attributed to asbestos in the next decades posed an additional question: What influence did the fibrous shape of the particles have on carcinogenic potential? The cogency of the problem was amplified by the identification in humans of asbestos-like neoplasms with a fiber other than asbestos (erionite) and by the production of such neoplasms in experimental animals with a variety of man-made inorganic fibers, often used as substitutes for asbestos. The lessons learned about asbestos may help guide us in evaluating current fiber problems.

Air Pollutants, Occupational↗

Immunohistochemical localization of transforming growth factor beta isoforms in asbestos-related diseases.

Transforming growth factor beta (TGF-beta), a multifunctional cytokine and growth factor, plays a key role in scarring and fibrotic processes because of its ability to induce extracellular matrix proteins and modulate the growth and immune function of many cell types. These effects are important in inflammatory disorders with fibrosis and cancer. The asbestos-related diseases are characterized by fibrosis in the lower respiratory tract and pleura and increased occurrence of lung cancer and mesothelioma. We performed immunohistochemistry with isoform-specific antibodies to the three TGF-beta isoforms on 16 autopsy lungs from Quebec, Canada, asbestos miners and millers. There was increased immunolocalization of all three TGF-beta isoforms in the fibrotic lesions of asbestosis and pleural fibrosis. The hyperplastic type II pneumocytes contained all three isoforms. By contrast, there was differential spatial immunostaining for the TGF-beta isoforms in malignant mesothelioma, with TGF-beta 1 in the stroma but TGF-beta 2 in the tumor cells. These data are consistent with an important role for TGF-beta in accumulation of extracellular matrix and cell proliferation in asbestos-related diseases.

Administration, Inhalation↗

Relative release of interleukin-1 beta and interleukin-1 receptor antagonist by alveolar macrophages. A study in asbestos-induced lung disease, sarcoidosis, and idiopathic pulmonary fibrosis.

We examined the influence of untreated interstitial lung disease (ILD) on the in vitro release of interleukin-1 beta (IL-1 beta) and interleukin-1 receptor antagonist (IL-Ira) from alveolar macrophages (AM); AM were harvested from normal volunteers, ILD patients, and patients with asbestos-related pleural disease but no ILD. AM were cultured for 24 h and assays for IL-1 beta and IL-1ra were done using sensitive and specific enzyme-linked immunosorbent assay. A greater amount of IL-1 beta was detected in AM supernatants from asbestosis, sarcoidosis, and IPF patients than in those from normal subjects. The IL-1 beta:IL-1ra ratio (IL-1 beta activity index [IL-1AI]) was significantly lower in supernatants of normal macrophages compared with macrophage supernatants from individuals with ILD. The IL-1AI correlated with bronchoalveolar lavage cellularity, a marker of disease activity. Current smoking was associated with lower IL-1 beta and IL-1ra release in ILD. The IL-1AI is a convenient method for comparison of IL-1 beta activity between patient populations.

Adult↗

Asbestos-induced pleural fibrosis and impaired exercise physiology.

To further assess the clinical significance of asbestos-induced pleural fibrosis, we performed cardiopulmonary exercise testing in 90 subjects who were exposed to asbestos. Of the 82 subjects without an abnormal resperate exercise, 35 had normal pleura, 33 had circumscribed pleural plaques, and 14 had diffuse pleural thickening. Interstitial fibrosis (International Labor Organization [ILO]. > or = 1/10) was present in 14 of 35 subjects with normal pleura, 13 of 33 subjects with circumscribed pleural plaques, and 2 of 14 subjects with diffuse pleural thickening. Although pleural fibrosis did not appear to be related to impaired respiratory function with exercise in our entire cohort, this finding was confounded by a higher proportion of interstitial fibrosis in subjects with normal pleura. In fact, among study subjects without asbestosis, significant decreases in gas exchange (higher VD/VT and increased alveolar-arterial oxygen pressure difference) were observed at maximal exercise among subjects with pleural fibrosis. Interestingly, neither a higher respiratory rate nor a lower VT/FVC ratio was observed among those with pleural fibrosis, suggesting that the mechanical effects of pleural fibrosis on the chest wall do not explain the increased VD/VT. Using multivariate analyses to control for potential confounders, regression models showed that pleural plaques (p = 0.04) and diffuse pleural thickening (p = 0.03) were independently associated with significant increases in dead space ventilation (VD/VT) with maximal exercise. These findings indicate that asbestos-induced pleural fibrosis is independently associated with decrements in gas exchange with maximal exercise and suggest that interstitial lung disease, not detected on the routine chest x-ray film, may be responsible for this abnormal response to exercise.

Asbestos↗

Environmental airborne tremolite asbestos pollution and pleural plaques in Afghanistan.

A 51-year-old man underwent pleuroscopy for radiologic pleural abnormalities. Pathologic examination of pleural and lung biopsy specimens concluded on hyalinized pleural plaques associated with mild asbestosis. Transmission electron microscopy analysis showed significant retention of tremolite asbestos fibers. The absence of any occupational exposure to asbestos and the existence of geologic deposits of tremolite in the Kabul area of Afghanistan suggest an environmental exposure during the patient's childhood spent in this region.

Afghanistan↗

Emphysema in silica- and asbestos-exposed workers seeking compensation. A CT scan study.

It has been established that coal pneumoconiosis and confluent silicosis are associated with emphysematous changes in the lungs. In the present study, we addressed the concept of emphysema in simple silicosis and asbestosis and in workers exposed to these minerals without the pneumoconiosis. The study was done on 207 consecutive workers evaluated for possible pneumoconiosis at Québec Workman Compensation Board, who had a radiographic reading of pneumoconiosis in the category 0 or 1 of the ILO scale, and in 5 control subjects. Emphysema was detected, typed, and graded on high-resolution CT scans by three independent experienced readers. Age, work experience and industry, smoking habits, and pulmonary function test results were analyzed for possible associations. The subjects were 59 +/- 1 years of age and had mineral dust exposure averaging 26 +/- 1 years; 31 were lifetime nonsmokers and the others were either ex- or current smokers. Ninety-six workers were from primary and 111 from secondary industries and did not differ in any parameter. The CT scan readings for emphysema yielded a 63% complete agreement. In lifetime non-smokers, emphysema was seen in 1 of 20 subjects without pneumoconiosis but in 8 of 11 patients with pneumoconioses. In smokers without pneumoconioses, emphysema was present in 55% of patients with silica exposure, but 29% of patients with asbestos exposure but comparable smoking (p = 0.04). Emphysema type was equally distributed among the groups except for more paracicatricial type in confluent silicosis. Regression analyses documented that age, smoking, exposure type, and presence of pneumoconiosis were significant contribution factors. In the workers without pneumoconiosis, age, smoking, and exposure type (silica) were significant. Emphysema related best with FEV1/FVC ratio, MMEF, and DCO reductions. The prevalence of abnormality of FEV1/FVC ratio was two to five times normal and that of reduced DCO two times normal. We conclude that, in our population, there was a significant excess of CT scan emphysema, associated with lung dysfunction, in those with pneumoconioses and in smokers with silica exposure. In the absence of smoking, it took a patient with pneumoconiosis to have emphysema. These changes contributed to the lung function impairment of these subjects with ILO category 0 or 1 pneumoconioses.

Analysis of Variance↗

Clara cell protein (CC-16) and surfactant-associated protein A (SP-A) in asbestos-exposed workers.

Asbestos-exposed workers (Asb) can sometimes develop lung impairments resembling idiopathic pulmonary fibrosis (IPF). Smoking is often a troubling confounder in the natural history of these lung diseases. Distal airspace epithelial cells, which are also altered in asbestosis, secrete Clara cell protein (CC-16, also designated CC-10) and surfactant-associated protein A (SP-A). By inhibiting phospholipase A2 (PLA2), CC-16 and SP-A are putative candidates for controlling lung inflammatory events. Both were measured with PLA2 activity in alveolar fluids (and sera for CC-16) of smoker and nonsmoker Asb and compared with smoking-matched normal subjects (N). CC-16 (in mg/L) was slightly increased in Asb and affected by smoking: nonsmoker Asb: 3.1 +/- 0.5 vs nonsmoker N: 1.9 +/- 0.2 (p < 0.05), smoker Asb: 1.7 +/- 0.3 vs smoker N: 0.6 +/- 0.1 (p < 0.05). SP-A (in microgram/mL) was enhanced in Asb but not affected by smoking: 5.4 +/- 1.5 in Asb vs 1.6 +/- 0.4 in N (p < 0.05), whereas SP-A to phosphorus ratio was increased in Asb but affected by smoking. CC-16 to albumin and CC-16 in serum to alveolar fluid ratios were altered by cigarette consumption in Asb (p < 0.05 vs N). Secretory PLA2 activity was slightly enhanced in Asb (p < 0.05 vs N). All data were similar between stages of disease. In summary, alveolar CC-16, SP-A, and secretory PLA2 activity were increased in Asb. Smoking affected several parameters. By this habit, Asb might reinforce lung profibrotic factors and increase their risk in developing lung alterations resembling IPF.

Adult↗

Pleural calcification associated with exposure to chrysotile asbestos in southeast Turkey.

In this study, pleural calcifications prevailing in the inhabitants of some villages and towns around Diyarbakir, a city in southeast Turkey, have been found to be caused by the inhalation of chrysotile asbestos, the mineral commonly used indiscriminately to paint the walls and floors of houses. There were no industrial establishments in the area, except some local mining, and asbestos deposits were even not included on the mining map of the country. Chest roentgenograms from the Chest Hospital and the tuberculosis dispensaries were screened: and, additionally, 15,239 photofluorograms were obtained during a survey. Of all these, 511 patients were found to have pleural calcifications, some with pericardial and diaphragmatic involvement. Forty-four percent (28) of the 64 patients who had examinations of samples of their sputa had asbestos bodies, and asbestosis was also induced in rabbits by administration of the raw material.

Adolescent↗

Observer agreement, chest auscultation, and crackles in asbestos-exposed workers.

Investigators cite observer variability as a problem in using crackles to diagnose asbestosis. We measured agreement on the presence or absence of crackles noted during auscultation of 64 asbestos-exposed workers in order to clarify this question. There was 89 percent agreement between two observers who simultaneously examined subjects breathing from functional residual capacity (FRC). Kappa (kappa), a statistic accounting for chance agreement, was 0.73. Unanimous agreement between four observers who listened to tape recordings of the breath sounds was 81 percent (kappa = 0.69). When the subjects breathed from residual volume (RV) there was 78 percent (kappa = 0.53) and 67 percent (kappa = 0.60) agreement, respectively. Comparing direct to tape-playback auscultation, there was 90 percent (kappa = 0.77) and 84 percent (kappa = 0.58) intraobserver agreement when the subjects breathed from FRC and 90 percent (kappa = 0.79) and 75 percent (kappa = 0.39) when they breathed from RV. We conclude that observer variability is sufficiently low to allow trained observers to monitor asbestos-exposed workers for crackles directly and during tape-playback auscultation.

Adult↗