Pleural plaques do not predict asbestosis: high-resolution computed tomography and pathology study

Pleural plaques can be caused by asbestos exposure, but their predictive value in diagnosing pulmonary asbestosis is uncertain. Similarly, although high-resolution computed tomography (HRCT) can accurately detect parenchymal lung lesions, its ability to detect asbestosis is unknown. In a test of the predictive value of pleural plaques and HRCT, lungs of 29 autopsied patients with bilateral parietal pleural plaques were compared with lungs from 29 age- and sex-matched controls without pleural plaques. Significantly more of the patients with pleural plaques had histories of asbestos exposure (P less than 0.01). One lung from each patient was inflation fixed and air dried. HRCT of the lungs did not show significantly more thickening, lines, or densities in patients with pleural plaques than did controls; and HRCT did not predict a significantly greater likelihood of asbestos-related parenchymal disease in the study group. Gross and histologic examinations showed no significant intergroup differences in the frequency or severity of several forms of emphysema and fibrosis. Average asbestos fiber counts were not significantly higher in the lungs with pleural plaques. We conclude that pleural plaques do not predict asbestosis, and that high-resolution computed tomography accurately detects interstitial and parenchymal lung disease but cannot reliably diagnose asbestosis.     

Cytopathology of asbestos-associated pulmonary disease

The goal of this investigation was to determine the practical role of cytopathology in the clinical and laboratory diagnosis of asbestos-related pulmonary diseases. For this purpose, sputum, bronchial washings, lung tissues, and pleural fluids were obtained from asbestos workers and controls. The asbestos-associated pulmonary diseases studied were: (1) asbestosis, (2) carcinoma, and (3) mesothelioma. The cytology smears were prepared with both Papanicolaou and iron stains. Lung tissues were digested by the Chlorox (5.25% sodium hypochlorite solution) technique for quantitation of asbestos bodies. Asbestos bodies within the sputum were found to be highly specific markers for past asbestos exposure, indicating a heavy residual pulmonary asbestos load (greater than 900 asbestos bodies/g wet lung weight). Asbestos bodies in sputum were also found to have a highly significant relationship (P less than 0.001) with the degree of accompanying atypia of bronchial epithelial cells. Bronchial washings appeared to be more sensitive than sputum for the detection of asbestos bodies. Asbestos bodies were not found within the pleural fluids of malignant mesotheliomas. It is concluded that sputum cytology screening represents a practical, noninvasive, and inexpensive approach to the diagnosis and study of asbestos exposure.     

Desmoplastic malignant mesothelioma of the pleura: autopsy reveals asbestos exposure

Desmoplastic mesothelioma is a rare subtype of diffuse malignant mesothelioma, and is often difficult to distinguish from reactive pleural fibrosis because of associated extensive collagen fibrosis. An 82-year-old woman with a severe cough was revealed to have pleural effusion and diffuse pleural thickening on the right side. Antibiotics were ineffective, and a compression fracture of the ninth and tenth thoracic vertebral bodies was recognized on X-ray. Autopsy revealed a diffuse pleural thickening with hyalinized collagen tissue in the central part of the pleura. However, the peripheral part of the fibrous tissue was composed of spindle and polygonal cell proliferation that were immunohistochemically positive for antibodies against cytokeratin and vimentin. In addition, the ninth and tenth thoracic spines were infiltrated by similar cells. The condition was diagnosed as desmoplastic mesothelioma with bone metastases. Asbestos bodies were detected in the thickened pleura and fibrosed alveolar septa, and it was suggested retrospectively that the patient had been exposed to asbestos. Thus, autopsy analyses of fibrous pleurisy are necessary to detect a desmoplastic variant of mesothelioma of the pleura and its association with asbestos exposure.     

Asbestos fibers and pleural plaques in a general autopsy population.

It has been claimed that symmetric lower zone pleural or diaphargmatic plaques are markers of asbestos exposure both in asbestos workers and the general population. In this study, total pulmonary asbestos burden was analyzed for 29 patients selected because pleural plaques were found at autopsy, and the results were compared with values obtained for 25 patients who had no occupational asbestos exposure. The average number of asbestos bodies in the plaque groups was 1732/g wet lung, and in the control group, 42/g wet lung. Uncoated asbestos fibers were extracted from lung and counted, measured, and identified by morphologic examination, electron diffraction, and energy-dispersive x-ray spectroscopy. The total number of fibers/per gram wet lung in the plaque group (114 x 10(3)) was similar to that in the control group (99 x 10(3), as was the number of chrysotile fibers (51 x 10(3) versus 29 x 10(3)). However, the plaque patients had a marked increase in the number of the commercially used high aspect ratio amphiboles, amosite and crocidolite (50 x 10(3) versus 1 x 10(3). A retrospective history of fairly certain asbestos exposure was obtained for 16 of the plaque patients, and such a history correlated strongly with increased numbers of commercial amphiboles in lung. It is concluded that 1) in this general autopsy population, two subgroups of patients are present. About one half of the patients appear to have developed pleural plaques as a result of asbestos exposure, while the etiology of the plaques in the other half is unclear; 2) the presence of pleural plaques correlates with a modest (50-fold) increase in numbers of long high-aspect ratio commercial amphiboles in lung tissue but does not correlate with numbers of chrysotile fibers, noncommercial amphiboles, or the total number of asbestos fibers; 3) asbestos-induced lesions are related to a complex set of mineralogic parameters and not to mere numbers of fibers in lung.     

Pathogenic effects of asbestos.

The enormous increase in the use of asbestos during this century has necessitated the intensive study of its pathogenic effects. The occurrence of pulmonary parenchymal and pleural fibrosis and an increased prevalence of pulmonary and gastrointestinal carcinoma and of pleural and peritoneal mesothelioma have been established. A relationship, also, to laryngeal carcinoma is probable. Mesothelioma has been associated with indirect occupational, domestic, and neighborhood exposure, and the possibility of a similar correlation of pulmonary carcinoma with low exposure has been suggested. Pulmonary fibrosis and pleural plaques have been demonstrated under these circumstances. The physical characteristics of the asbestos fiber appear to be the principal factors in its carcinogenic action. The ability of fine, short fibers, especially fragmented chrysotile, to reach the pleura would appear to account for many of the pathogenetic and anatomical features of asbestos-related disease.     

Effect of platelet-derived growth factor on the development and persistence of asbestos-induced fibroproliferative lung disease.

Platelet-derived growth factor (PDGF) isoforms and PDGF receptor-alpha are upregulated in fibroproliferative lesions in response to asbestos exposure. To examine the functional role of PDGF in asbestos-induced lung disease, we have evaluated the impact of PDGF-B overexpression in the lung on the development of pulmonary fibrosis induced by asbestos inhalation. Transgenic mice expressing PDGF-B from the surfactant protein C promoter and wild-type C57BL/6 mice were exposed to aerosolized chrysotile asbestos fibers via three different exposure regimens: 3 consecutive days to 9 mg/m(3), once a week for 5 weeks to 12 mg/m(3), or once a week for 8 weeks to 11 mg/m(3). The 3-day exposure did not produce fibroproliferative lesions in SPC-PDGFB or wild-type mice, indicating that PDGF expression did not increase susceptibility to a subthreshold dose of asbestos. Transgenic and wild-type mice subjected to the 5-week exposure protocol exhibited similar fibrogenic lesions histologically 48 hours and 8 weeks postexposure, but lungs from transgenic mice had elevated lung hydroxyproline content 8 weeks postexposure relative to wild-type mice. In addition, SPC-PDGFB transgenic mice developed pronounced thickening of arterioles following the 5-week exposure regimen. Mice exposed to asbestos for 8 weeks and examined 10 months later showed pronounced, diffuse fibrotic lesions of terminal bronchioles and alveolar ducts, but no histological differences between transgenic and nontransgenic mice were observed. These results indicated that PDGF-B overexpression can stimulate increased collagen deposition and vascular smooth muscle hyperplasia following asbestos inhalation and that a limited exposure (8 times) to chrysotile aerosol can produce long-lasting fibrotic lesions. The 8-week exposure regimen provides an animal model that encompasses an important aspect of human asbestosis-i.e., persistence of fibrosis for long periods after cessation of asbestos exposure.     

Controversies and uncertainties concerning the pathologic features and pathologic diagnosis of asbestosis.

Asbestos is a fibrous silicate mineral that has been known for decades to cause pulmonary scarring, referred to as asbestosis. The simplest definition of asbestosis is the presence of pulmonary fibrosis as a result of accumulation of airborne asbestos in the lungs. Not infrequently, the terms "asbestos" and "asbestosis" are used incorrectly (interchangeably) by medical personnel, and sometimes pleural fibrosis caused by asbestos is incorrectly referred to as asbestosis. The earliest lesion of asbestosis, as defined by the CAP-NIOSH Committee is peribronchiolar fibrosis, although controversy exists as to how specific this lesion is with respect to causation by asbestos, and whether this lesion progresses to grade 4 asbestosis. In addition, some authorities in the field suggest that the term "asbestosis" be used only for diffuse interstitial fibrosis. The mechanism by which asbestos causes interstitial fibrosis remains poorly understood, and in recent years, pathologic changes such as organizing pneumonitis-bronchiolitis obliterans, and lymphocytic interstitial pneumonitis, have been described in persons occupationally exposed to asbestos, suggesting that the pulmonary lesions caused by asbestos represent a wider spectrum than had previously been appreciated. By defining areas of uncertainty, medical science will eventually clarify areas of disagreement concerning asbestosis which will eventually lead to a better understanding of this disease.     

Intrapulmonary distribution of inhaled chrysotile and crocidolite asbestos: ultrastructural features.

Although all commercial types of asbestos can cause pulmonary fibrosis, little is known about ultrastructural differences in the evolution of pulmonary lesions induced by amphiboles and serpentines. The present study was designed to compare the histological and ultrastructural effects produced by chronic inhalation of either crocidolite (amphibole) or chrysotile (serpentine) asbestos in the rat. Animals, exposed by intermittent inhalation for 3 months, were killed after 2 to 16 months. When inhaled, both types of asbestos caused thickened alveolar duct bifurcations associated with macrophage aggregates. Crocidolite inhalation also produced subpleural collections of alveolar macrophages and lymphocytes. Electron microscopy revealed some similarities, but also distinct differences, in the pulmonary distribution of inhaled chrysotile and crocidolite. Whereas both asbestos varieties were identified within the pulmonary interstitium, only crocidolite was detected inside alveolar macrophages. Chrysotile fibres were seen infrequently within the vascular compartment. Microcalcifications were noted after chrysotile inhalation, but were never observed following crocidolite exposure. Both asbestos types induced slight pulmonary fibrosis. These findings indicate that crocidolite and chrysotile produce different pathogenetic features, although both are fibrogenic.     

Intrapulmonary distribution of inhaled chrysotile and crocidolite asbestos: ultrastructural features

Although all commercial types of asbestos can cause pulmonary fibrosis, little is known about ultrastructural differences in the evolution of pulmonary lesions induced by amphiboles and serpentines. The present study was designed to compare the histological and ultrastructural effects produced by chronic inhalation of either crocidolite (amphibole) or chrysotile (serpentine) asbestos in the rat. Animals, exposed by intermittent inhalation for 3 months, were killed after 2 to 16 months. When inhaled, both types of asbestos caused thickened alveolar duct bifurcations associated with macrophage aggregates. Crocidolite inhalation also produced subpleural collections of alveolar macrophages and lymphocytes. Electron microscopy revealed some similarities, but also distinct differences, in the pulmonary distribution of inhaled chrysotile and crocidolite. Whereas both asbestos varieties were identified within the pulmonary interstitium, only crocidolite was detected inside alveolar macrophages. Chrysotile fibres were seen infrequently within the vascular compartment. Microcalcifications were noted after chrysotile inhalation, but were never observed following crocidolite exposure. Both asbestos types induced slight pulmonary fibrosis. These findings indicate that crocidolite and chrysotile produce different pathogenetic features, although both are fibrogenic.     

亲属活体肾移植供者移植前行肺部CT检查的必要性

背景：亲属肾移植供者年龄较大会有一定肺部疾病发病率。 目的：了解亲属活体供者肺部疾病的发生率进而探讨亲属活体供者移植前行肺部CT检查的必要性。 方法：纳入郑州大学第一附属医院自2009-07/2011-04拟行亲属供肾切取的127例亲属肾移植供者,排除捐献禁忌证如高血压、糖尿病及供受者血型不符后,常规行胸部CT及X射线检查。由2位放射科医师结合临床表现讨论后对胸部CT及X射线结果作出诊断,评价肺部检查结果对供肾移植的影响。 结果与结论：127例供者常见肺部疾病依次为肺炎(15.0%)、肺气肿(7.9%)、肺实质钙化(6.3%)、胸膜增厚(3.1%)、胸膜粘连(3.1%)。除钙化外肺部CT检查比X射线可以更敏感的监测出各种肺部疾病(P < 0.05)。此外,供者肺炎冬季发生率比夏季高(P < 0.05),有吸烟史供者肺气肿发生率高于无吸烟史供者(P < 0.01)。绝大多数肺部疾病并不影响活体供肾手术的进行,仅有1例治疗无效的间质性肺炎供者放弃手术。结果证实,肺部疾病在亲属肾移植供者中有较高发生率,有吸烟史或手术安排在冬季进行的供者移植前有必要行CT检查。     

Bronchiolitis obliterans-organizing pneumonia (BOOP) containing asbestos bodies: clinico-pathological study of a case]

We describe a case of bronchiolitis obliterans-organizing pneumonia (BOOP) with asbestos bodies. A 65-year-old man, treated in the past for gastric lymphoma and with an history of asbestos exposure, presented with fever and two nodular opacities in the lower lobe of the left lung. Histologic examination revealed a BOOP pattern; in the inflammatory tissue some asbestos bodies were present. Patients exposed to asbestos may rarely present with localized inflammatory pulmonary lesions. In these cases, the possible etiopathogenetic role of asbestos needs further studies.     

Idiopathic pulmonary fibrosis vs. pulmonary involvement of collagen vascular disease: HRCT findings.

The purpose of this study is to assess the differences of high-resolution CT (HRCT) findings in patients with idiopathic pulmonary fibrosis (IPF) and pulmonary involvement of collagen vascular disease (CVD). We analyzed the HRCT findings of 33 patients with IPF and 23 patients with CVD in terms of predominant pattern, site of involvement, mediastinal lymph node enlargement, pleural change, and pulmonary volume loss. The predominant HRCT pattern was honeycombing for IPF (58%), and ground-glass opacity for CVD (57%). Predominantly subpleural involvement was seen in 90% of IPF and 83% of CVD patients. Mediastinal lymph node enlargement was seen in 61% of the patients with IPF and 13% with CVD (p = 0.0004). Pleural thickening was seen in 97% of the patients with IPF and 35% with CVD and the severity of pleural thickening is statistically significant (p = 0.00001). Pleural effusion was seen in 6% of the patients with IPF and 26% with CVD (p = 0.0351). The hilar height ratio was more than 1.5 in 52% of the patients with IPF and 30% with CVD (p = 0.2620). Although HRCT findings of IPF and pulmonary involvement of CVD are similar and overlap considerably, but patients with IPF showed a tendency to more progressed fibrosis than patients with CVD.     

PSEUDOMESOTHELIOMATOUS CARCINOMA OF THE LUNG WITH HISTOCHEMICAL AND IMMUNOHISTOCHEMICAL STUDY

An autopsy case of pseudomesotheliomatous carcinoma of the right lung in a 56–year–old man occupationally exposed to stone dust is presented. From open biopsy specimens in which polyhedral epithelium–like cells appeared arranged in nests, sheets, and trabecula without apparent tubular pattern, a malignant pleural mesothelioma was suspected. At autopsy, the right pleural cavity was obliterated by the tumor mass which covered the collapsed pulmonary parenchyma and was clearly demarcated from it. The gross appearance of the tumor was similar to that of malignant pleural mesothelioma. Histologically, marked Interstitial fibrosis of the subpleural parenchyma of both lungs was observed, and the tumor tissue was interspersed in the parenchyma adjacent to the tumor mass. The tumor showed both intracytoplasmic and intercellular positive materials with colloidal iron, alcian blue (pH 2.5), and toluidine blue stains, which entirelly disappeared after streptomyces hyaluronidase digestion. A small amount of intracytoplasmic PAS–positive material resistent to diastase digestion was also observed. Immunohlstochemical staining for carcinoembryonic antigen, which is said to be negative in malignant pleural mesothelioma, was positive intracellularly. There were no histologic findings indicating asbestos exposure. From these findings, the authors made a diagnosis of poorly differentiated adenocarcinoma, which was characterized by the production of hyaluronic acid. ACTA PATHOL. JPN. 33: 415–423, 1983.     

Increased localization and substrate activation of protein kinase C delta in lung epithelial cells following exposure to asbestos

The protein kinase C (PKC) family consists of several isozymes whose substrates may be necessary for the regulation of key cellular events important in the pathogenesis of proliferative diseases. Asbestos is a carcinogen and fibroproliferative agent in lung that may cause cell signaling events through activation of PKC. Here we used a murine inhalation model of asbestos-induced inflammation and fibrosis to examine immunoreactivity of PKC delta and its substrate, phosphorylated-adducin (p-adducin), in cells of the lung. Moreover, we characterized PKC delta and p-adducin expression in a pulmonary epithelial cell line (C10) in both log versus confluent cells and in cells after mechanical wounding or crocidolite asbestos exposure. Both PKC delta and p-adducin were almost exclusively expressed in bronchiolar and alveolar type II (ATII) epithelial cells in lung sections and increased in these cell types after inhalation of asbestos by mice. Increases in membrane and nuclear localization of PKC delta were seen in log phase as compared to confluent C10 cells. Moreover, enhanced immunoreactivity of PKC delta was observed in epithelial cells expressing proliferating cell nuclear antigen (PCNA) after mechanical wounding or exposure to asbestos fibers. These studies show that activated PKC delta in pulmonary epithelial cells is a consequence of inhalation of asbestos and may be linked to the activation of cell proliferation.     

百草枯中毒致肺损伤的CT表现

目的探讨百草枯中毒致肺损伤中的CT检查影像学特征和诊断价值。方法回顾性分析15例口服百草枯中毒致肺损伤病例的CT影像学资料。结果15例患者中毒早期（1～7d）主要CT表现包括支气管血管柬增粗伴支气管扩张显示轨道征（15／15）、磨玻璃密度影（14／15）、马赛克征（12／15）、树芽征（8／15）、肺实变（6／15）及胸膜下线（6／15）等；中毒中期（8～14d）主要表现支气管血管束增粗伴支气管扩张显示轨道征（11，11）、肺实变（7／11）及磨玻璃密度影（6／11）；中毒后期（〉14d）CT表现以肺实变（1／1）和纤维化（1／1）为主。结论百草枯中毒的肺部CT表现具有一定的特征性，其影像学变化对病情发展及指导临床治疗具有重要意义。     

Lung cancer and past occupational exposure to asbestos. Role of p53 and K-ras mutations

Studies on somatic mutations in lung cancers associated with cigarette smoking and asbestos exposure are few. We investigated prevalence of mutations in the p53 and K-ras genes in lung tumors from smokers with and without asbestos exposure at work. For K-ras mutations, the study was an extension of an earlier analysis. Nearly all of the 105 consecutive patients examined were smokers and had non-small-cell carcinoma of the lung with squamous-cell carcinoma or adenocarcinoma histology. Exposure to asbestos was estimated by pulmonary fiber counts and occupational histories. A pulmonary burden of >/= 1 x 10(6) asbestos fibers per gram of lung tissue, indicating work-related exposure, was found in 32% of the patients for whom fiber-analysis data were available (33 of 102 patients, all men). The statistical analysis showed pulmonary fiber count as the only significant predictor of adenocarcinoma histology, in contrast to squamous-cell carcinoma (smoking-adjusted odds ratio [OR] 3.0, 95% confidence interval [CI] 1.1 to 8.5). The frequency of p53 mutations was 39% (13 of 33) among the asbestos-exposed cases, as compared with 54% (29 of 54) among the nonexposed cases; the difference was not significant, however. In male ever-smokers, a long duration of smoking was associated with p53 mutation (OR 3.2, 95% CI 1.2 to 8.8). In adenocarcinoma, p53 mutations were less prevalent (10 of 30, 33%) as compared with squamous-cell carcinoma (28 of 46, 61%; P = 0.02), whereas a strong and significant association was found between adenocarcinoma and K-ras mutation (OR 37, 95% CI 5.8 to 232, adjusted for smoking and asbestos exposure). Asbestos exposure alone was not significantly associated with increased occurrence of K-ras mutations. In conclusion, the results may primarily reflect the observed excess of adenocarcinoma in the asbestos- exposed patients, and hence the decrease in p53 mutations and increase in K-ras mutations.     

Experimental studies in rats on the effects of asbestos inhalation coupled with the inhalation of titanium dioxide or quartz.

Rats were exposed for 1 year, with a 2-year follow-up, to dust clouds consisting of a mixture of amosite or chrysotile asbestos with either titanium dioxide or quartz. The addition of titanium dioxide to asbestos did not increase levels of pulmonary fibrosis above the amounts produced by chrysotile or amosite alone. Quartz, however, greatly increased fibrosis above that produced by the asbestos types alone. Both particulate dusts caused an increase in the numbers of pulmonary tumours and mesotheliomas compared to asbestos alone but while tumours in animals treated with asbestos and quartz tended to occur earlier than tumours with asbestos alone, in animals treated with dusts containing titanium dioxide, tumour production occurred later than with asbestos alone. In animals treated with mixtures of asbestos and quartz, there was evidence of increased transport of fibres across the visceral pleural surface and this may be associated with the finding of a higher proportion of pleural mesotheliomas than previously reported in experimental inhalation studies from any laboratory using the main asbestos varieties. The presence of particulate dusts made little difference to the amounts of amosite fibre retained in the lung tissue but, with chrysotile, titanium dioxide appeared to increase retention while quartz reduced it.     

HLA—A and B Antigen Frequencies in an Asbestos Exposed Population with Normal and Abnormal Chest Radiographs

Previous studies of HLA antigen frequencies in asbestos related pulmonary fibrosis have suggested some weak associations both with susceptibility to the disease (B12 and B27) and protection from the disease (B18 and Bw35). HLA typing was performed on a further series of 64 asbestos workers with no chest abnormality and 166 workers with various radiographic changes, 78 having pulmonary fibrosis. The results fail to give statistical confirmation of these associations although B27 was twice as frequently associated with pulmonary fibrosis and diffuse pleural thickening. Analysis of the combined data from this and four other studies failed to show any consistent associations.