Associations of polymorphisms in the cytokine genes IL1ß (rs16944), IL6 (rs1800795), IL12b (rs3212227) and growth factor VEGFA (rs2010963) with anthracosilicosis in coal miners in Russia and related genotoxic effects.

Anthracosilicosis (AS), a prevalent form of pneumoconiosis among coal miners, results from the accumulation of carbon and silica in the lungs from inhaled coal dust. This study investigated genotoxic effects and certain cytokine genes polymorphic variants in Russian coal miners with АS. Peripheral leukocytes were sampled from 129 patients with AS confirmed by X-ray and tissue biopsy and from 164 asymptomatic coal miners. Four single-nucleotide polymorphisms were genotyped in the extracted DNA samples: IL1ß T-511C (rs16944), IL6 C-174G (rs1800795), IL12b A1188C (rs3212227) and VEGFA C634G (rs2010963). Genotoxic effects were assessed by the analysis of chromosome aberrations in cultured peripheral lymphocytes. The mean frequency of chromatid-type aberrations and chromosome-type aberrations, namely, chromatid-type breaks and dicentric chromosomes, was found to be higher in AS patients [3.70 (95% confidence interval {CI}, 3.29-4.10) and 0.28 (95% CI, 0.17-0.38)] compared to the control group [2.41 (95% CI, 2.00-2.82) and 0.09 (95% CI, 0.03-0.15)], respectively. IL1ß gene T/T genotype (rs16944) was associated with AS [17.83% in AS patients against 4.35% in healthy donors, odds ratio = 4.77 (1.88-12.15), P < 0.01]. A significant increase in the level of certain chromosome interchanges among AS donors is of interest because such effects are typical for radiation damage and caused by acute oxidative stress. IL1ß T allele probably may be considered as an AS susceptibility factor among coal miners.

Specificity of morphologic changes in target organs, associated with exposure to coal rock dust and fluorine compounds.

The studies revealed specificity of morphologic changes in target organs, depending on acting occupational hazard. Evidences are that inhalation of coal rock dust causes irreversible sclerotic and degenerative changes mostly in lungs and bronchi even on 6th week of the experiment. In liver, changes in parenchyma and stroma are controlled by reparative processes by 9th week. Accumulation of sodium fluoride in the body causes irreversible necrotic changes mostly in liver, on 6th week of the intoxication. With that, morphologic changes in lungs and bronchi are minor, characterized by immune inflammation with degenerative changes only after the 9th week. Irrespective of the acting hazard, vascular changes are characterized by media and intima hypertrophy with endothelial dystrophy and hyalinosis since the 6th week of the experiment.

Experimental Study of the Mechanisms of Intracellular Defense in Cardiomyocytes Associated with Stages of Anthracosilicosis Development.

Mechanisms of intracellular defense of rat cardiomyocytes were studied in dynamics of anthracosilicosis development induced by long-term inhalation of coal and rock dust. It was shown that synthesis of transcription factor HIF-1α and protective proteins increased in the heart at the early stages of coal and rock dust inhalation (1-3 weeks), and these changes limited the development of free radical oxidation and activated metabolism of glucose and fatty acids. Exposure to coal and rock dust for 6-12 weeks activated free radical oxidation and decreased basal metabolism in cardiomyocytes.

[Quantitative characteristics of pathomorphologic changes in bronchi and pulmonary artery branches in miners with preroentgenologic stage of anthrasilicosis].

Morphometric studies covered lung tissue of 10 miners exposed to dusty work conditions over 1 to 30 (13.4 +/- 3.6) years, who were considered apparently healthy according to follow-up examinations and died in technogenic accident. Findings are that dysregeneration, hypertrophic and sclerotic changes in respiratory part of lungs, in bronchi and in pulmonary circuit arteries develop simultaneously--that proves common pathogenetic concept of these changes and systemic character of the pneumoconiosis. The results necessitate improved methods to evaluate health state of workers, refined criteria for nosologic diagnosis of respiratory diseases related to dust.

[Charcoal smoke causes bronchial anthracosis and COPD]. / Holzkohlefeuer als Ursache von bronchialer Anthrakose und COPD.

BACKGROUND: Bronchopulmonary disease due to inhalation of smoke from open woodfires represents a major health problem in developing countries. Due to increasing migration such patients also present to medical services in Europe. CASE REPORT AND DISCUSSION: An 84-year-old Afghan housewife who never smoked nor has a history of exposure to inorganic dusts, presents with chronic obstructive pulmonary disease (COPD) in association with bronchial anthracosis and stenosis of a bronchus. The complaints are found to be caused by chronic inhalation of smoke from an open woodfire which was used for cooking. The main complaints of "woodsmoke-associated lung disease" are cough und dyspnea with bronchial obstruction. Radiology and bronchoscopy usually reveal changes which are similar to pneumoconiosis of miners but without patients' relevant exposure. There is a frequent association of anthracotic bronchial stenosis and infection with tuberculosis. CONCLUSION: Since patients rarely recognize the risks of woodsmoke inhalation, they hardly report their exposure. Thus, the anamnesis is crucial to establish the right diagnosis and guide the patient to the appropriate diagnostic and therapeutic procedures.

Rapid Growth of Lung Nodules due to Combined Pulmonary Vasculitis, Silicoanthracosis, and Chondrocalcinosis.

Background. Silicoanthracosis is a pneumoconiosis due to occupational inhalation of silica and carbon dusts. Clinically, it can be associated with vasculitis or rheumatoid arthritis. In association with these diseases, silicoanthracosis can present within the lung with multiple pulmonary nodules which, as a differential diagnosis, can mimic metastatic disease or multiple abscesses. Case Presentation. We present the case of a 62-year old former pit worker with pulmonary nodules, chondrocalcinosis due to calcium pyrophosphate deposition (CPPD), and a history of renal cancer. Within a short period of time, pulmonary nodules grew rapidly. Thoracoscopically, the resected lung specimen revealed silicoanthracosis associated with small-to-medium-size vasculitis in the presence of antineutrophil cytoplasmatic autoantibodies (c-ANCA). Conclusion. Pulmonary silicoanthracotic lesions on the base of ANCA-associated vasculitis and CPPD arthritis can rapidly grow. A mutual correlation between silicoanthracosis, ANCA-associated vasculitis, and CPPD seems possible. Apart from this, consideration of metastatic disease should be obligatory in patients with a history of cancer at the same time being immunosuppressed.

A case report of anthracosilicotic spindle-cell pseudotumor of mediastinal lymph node: cytologic diagnosis by endoscopic ultrasound-guided fine-needle aspiration.

Pigmented spindle-cell tumors of the lymph nodes have a broad differential diagnosis, including both benign and malignant neoplasms. Here, we report a case of a pigmented spindle-cell lesion in a mediastinal lymph node mimicking a spindle-cell melanoma on fine-needle aspiration cytology. Smears showed atypical polygonal and spindle cells with bland nuclear features and abundant cytoplasmic anthracotic pigment. Immunohistochemistry was negative for melanoma markers, but showed positivity for histiocyte markers. Polarization microscopy revealed minute birefringent intracellular crystals consistent with silica. Electron microscopy was confirmatory and a diagnosis of anthracosilicotic spindle-cell pseudotumor was made. To the best of our knowledge, fine-needle aspiration cytology findings of this lesion have not been reported.

[A clinicopathological study of 16 autopsy cases of anthracosilicosis with lung cancer].

OBJECTIVE: To investigate the clinicopathological characteristics of anthracosilicosis complicated with lung cancer. METHODS: Tissue specimens from 16 autopsy cases of 0(+) anthracosilicosis complicated with lung cancer were retrospectively studied by hematoxylin-eosin, histochemical, and immunohistochemical staining. RESULTS: All of 16 patients were male. The patient's age ranged from 46 to 57 years (average: 52.8 years). The dust-exposure time were over 25 years. The pneumoconiosis and dust fibrosis of different degrees in the lung were found. The positive detected rate of coal silicotic nodules was 93.75% (15/16). Among 16 cases of lung cancer, there were 5 cases of squamous cell carcinoma, and 5 cases of small cell undifferentiated carcinoma, 3 cases of bronchioloalveolar carcinoma, 2 cases of adenocarcinoma and 1 case of adenosquamous carcinoma. The typical pathological changes of anthracosilicosis complicated with lung cancer were: the cancer tissue was located at the side of coal dust fibrous focus and fibrosis lesion, or mixte with silicotic lesion. CK, EMA and CEA were positively expressed in most of the tumor cells, while vimentin was positive in the fibrocyte of dust fibrosis. CONCLUSIONS: The occurrence of some lung cancer may be related with fibrosis. The dust-exposed workers can suffer from lung cancer which is histologically identical to the general lung tumor. PCNA and Ki67 may be a prognostic index for anthracosilicosis with lung cancer, while vimentin may be a marker for the examination of dust fibrosis in anthracosilicosis.

Anthracotic and anthracosilicotic spindle cell pseudotumors of mediastinal lymph nodes: report of five cases of a reactive lesion that stimulates malignancy.

We report five cases of reactive mediastinal spindle cell proliferations associated with anthracosis and anthracosilicosis that simulated a malignant process both on clinical and morphological grounds. Clinically, the lesions formed radiographically evident masses or were infiltrative. Microscopically, a prominent storiform pattern of intertwining spindle cells was found in four cases. This proliferation extended outside of the lymph node capsule in three cases and surrounded nerves in two. Because of this combination of features, the submitted diagnoses included a malignant neoplasm in four cases. The spindle cells were immunoreactive for histiocytic markers and focally contained fine anthracotic pigment. All cases featured nodular hyaline scars and contained polarizable material suggestive of silica, although a history of industrial exposure was obtained in only two cases. No lesion has enlarged or otherwise progressed during follow-up ranging from 6 to 48 months. The differential diagnosis includes a variety of spindle cell neoplasms, including malignant fibrous histiocytoma, follicular dendritic cell tumor, spindle cell melanoma, and Kaposi's sarcoma.

Effect of simple anthracite pneumoconiosis on lung mechanics.

A respiratory questionnaire was administered to 20 miners with simple anthracite coal workers' pneumoconiosis (CWP) and ten normal subjects. Lung function studies which included lung mechanics and small airways disease measurements were also performed. Seventeen of the miners admitted to having symptoms of bronchitis. No significant differences were demonstrated between the two groups for vital capacity (VC), forced vital capacity (FVC), forced expiratory volume in one second (FEV1), and three seconds (FEV3), midmaximal flow rate (FEF25-75%), and peak flow rate (PEFR). A significant decrease in the maximum expiratory flow rate at 50 percent of vital capacity (V max50%) was detected; however, this was not evident when the flow rate was corrected for lung volume. Also, there were no significant differences in lung volumes, diffusing capacity (DCO) and diffusion coefficient (DCO/TLC). The mean static expired compliance (Cstate) was significantly increased in the anthracite miners, but no difference in specific compliance (Cstate/FRC) could be demonstrated. Also, no significant differences were detected in the mean values of any of the tests of small airways disease. There is little evidence of significant alterations in lung mechanics or small airway narrowing in miners with simple anthracite pneumoconiosis.

Pulmonary arteriolar muscularization in coal workers' pneumoconiosis and its correlation with right ventricular hypertrophy.

The relationship between the thickness of the walls of small pulmonary arteries (the medial wall thickness as a percentage of external diameter, percentage of medial thickness) in coal miners and control subjects were studied using morphometric techniques and correlated with the degree of right ventricular hypertrophy, severity of coal workers' pneumoconiosis, emphysema, and other chronic lung diseases. Pulmonary arteries less than 100 microns in external diameter were identified and the external diameter, medial thickness, and intimal thickness were quantitatively measured in the lung tissues of 57 coal miners and 15 control subjects with and without other chronic lung diseases. Coal workers' pneumoconiosis, emphysema, and right ventricular hypertrophy were assessed uniformly in all cases. The arterial wall thickness correlated with right ventricular hypertrophy, progressive massive fibrosis, and other chronic lung diseases. Severity of emphysema also showed a weak correlation. Although the functional significance of these findings is not known, we conclude that the muscularization of pulmonary arterioles provides a structural basis for the development of right ventricular hypertrophy in coal miners.

[Discontinuous lymph node metastases ("skipping") in malignant lung tumors]. / Diskontinuierliche Lymphknotenmetastasen ("skipping") bei bösartigen Lungentumoren.

In 50 lung cancers (25 small cell lung cancers, 17 squamous cell carcinomas, 8 adenocarcinomas) pulmonary, mediastinal and cervical lymph node-metastases were analyzed. Lymph-node "skipping" was demonstrated in 46% of the investigated tumors. In seven of these cases the lymph nodes were skipped, which showed complete hyalinization as a consequence of preexisting anthracosilicosis. In 5 other tumors additional lymph nodes with preserved structure were skipped by the metastatic process. Fibrosis of lymphatic tissue after tuberculosis or exposure to ionizing radiation were further reasons for lymph-node skipping. The skipping of intact lymph nodes can be explained by anatomically demonstrable intra- and perinodal short circuit connections. Apart from that, preexisting lymph node changes (silicosis, fibrosis) play an important part.

[Determination of dust content in the lungs of 10 cases with stage I coal workers' pneumoconiosis (CWP)].

Dust deposition in the lung tissue of 10 cases with pathologically diagnosed stage I CWP was determined. The left lung tissue was digested by 37% hydrochloric acid, and its organic composition was removed by chloroform and 50% ethanol. Results showed total dust content averaged 8.64 grams per left lung, with a standard deviation of 5.54 grams. Dust content varied in different parts of the lung, measured the highest in lymph nodes, the upper lobe and pleura the next and the lowest in the lower lobe, with a very significant difference by ANOVA (F = 44.76, P < 0.001). Dust less than 5 microns in diameter accounted for 94.0% of the total content, and that equal to or more than 10 microns only 0.8%. A certain amount of fibrous dust could be found in the lung. Dust deposited in the lung accounted only for 0.64% of that exposed to.

[Pathological observations on massive fibrosis of coal-mine pneumoconiosis].

Morphological studies on massive pulmonary fibrosis due to pneumoconiosis in 42 cases were performed. The cases were divided into two types: the coalescence of fibrotic nodules type and the progressive massive fibrosis type. The former includes fusion of simple silica or coal-silica nodules and coalescence of mainly coal-silico-tubercle nodules. When pneumoconiosis is complicated by tuberculosis, the coal-silico-tubercle is the pathological change caused by the combination of dust and inflammation. The resulting conglomerate mass can be classified as progressive massive fibrosis. A comparison of micro-element content between non-massive fibrosis and massive fibrosis was made, and only the silicon content showed a significant difference (P < 0.05). The morphology, pathogenesis and formation of progressive massive fibrosis are discussed.

[Clinical application of ultra-thin bronchofiberscope examination].

Ultra-thin bronchofiberscope examination has been performed in 73 persons including normal persons and patients with various bronchopulmonary disease. The main lesions of peripheral airways revealed by the examination were reddening, pigmentation, secretion, engorgement of blood vessels, mucosal pallor and edema. The result points out that this is a valuable new technique in the diagnosis of small airway lesions, especially the diffused inflammatory of small airways. In case of a localized lesion, because of the difficulty to precisely determine the site, the effectiveness of this examination is limited. We also briefly discussed the matters that one should pay attention to while performing this technique.

[Application of polarized microscopy and analytic electron microscopy in pneumoconiotic pathologic examination].

38 cases of pneumoconiotic pathologic slides have been reexamined by polarized microscopy, among this, 3 cases (every 1 case of silicosis, asbestosis, cement dusts pneumoconiosis) have investigated by analytic electron microscopy. Authors presented, crystal silica and asbestos fiber may be showing under polarized light, and often associated with carbon dusts or fibrotic proliferation. So that, polarized microscopy may be as a preliminary detect method for silica and uncoated asbestos fiber from histologic slide, according to its dimension, color, lightness, morphologic feature and position were differential diagnosis from other positive substance under routine pathologic examination, further demonstration must to be reduced to ashes and re-observation under polarized microscopy. Also we selected 3 cases of silicosis, asbestosis, cement dusts pneumoconiosis specimen prepared to ultramicrotomic slides and examined by H-800 electron microscopy, when discovered some particles (such as crystal, non-crystal or fibrotic dusts) in cytoplasm of macrophages or interstitial space then used EDAX estimated. Its elements distribution were conformity with dusts (silica, asbestos, cement dusts).

[An comparative analysis of the radiographic appearances and the pathologic findings in anthracosilicosis and anthracosilicosis associated with tuberculosis].

Pulmonary tuberculosis is a serious complication of anthracosilicosis and a promoting factor for death. It is very difficult to distinguish the advanced stage of atypical anthracosilicosis from anthracosilicosis associated with tuberculosis by the chest radiograph when the tubercule bacili is negative in sputum, but it is necessary for physician to treat and administrate. In order to probe into the differential diagnosis of these two diseases author made a comparison analysis between the radiographic appearances and the pathological findings of 21 autopsies cases which were clinically diagnosed as anthracosilicosis associated with tuberculosis. There were 8/21 cases (38.1%) of misdiagnosis before the misdiagnosis there were the lack of series observation on the similarities and differences in radiographic appearances between these two diseases and neglect of sputum examination. The main points of clinical differentiation between them were summed up.

[Biological testing of the fibrogenic effect of dust from the "Sosnowiec" mine on the lung tissue]. / Biologiczny atest zwlókniajacego dzialania pylów z kopalni "Sosnowiec" na tkanke plucna.

In order to determine biological aggressiveness of settled dusts (mechanical, crumbled) and dusts collected using the gravimetric method, experimental studies were carried out, including: 1) evaluation of the physicochemical parameters (size of dust particles, content of silica, metals and other chemical compounds), 2) evaluation of the haemolytic activity, 3) experimental evaluation of fibrogenic potentials by means of: a) intraperitoneal test--to identity morphological type of reactive changes in the peritoneum and b) intratracheal test--to determine the level of hydroxyproline (collagen) in lungs and the morphological type of reactive changes. Albino rats were used for the experiment. The animals were divided into ten groups which received a single intratracheal injection of 50 mg of mining dust in 0.9% NaCl suspension. Comparative evaluation of biological aggressiveness of mining dusts was conducted basing on the findings of collagen levels in lungs. After the end of the experimental period (3 and 6 months, respectively) histopathological a examination of the lungs and mediastinal lymph nodes was made and the collagen levels in the pulmonary tissue (following Stegemann) were determined. As evidenced by the results of the pathomorphological examination and a statistical analysis: 1) after intratracheal injection the mining dusts induced changes within the respiratory system e.g. inflammatory process and emphysema. The exposure also brought about double increase of collagen level as compared to the control group, 2) histopathological study of the lungs and lymph nodes did not reveal progressive development of fibrogenic changes, 3) cytotoxic test showed differences in the haemolytic activity of settled dust and dusts collected by the gravimetric method.

The influence of dust originated in different coal mines on pneumoconiotic changes in white rats.

In experiments on white rats, three different types of dust of equal dispersion, coming from coal mines, were examined. The dusts exhibited different content of free silica and certain metals, such as: nickel, chromium and vanadium. The animals intratracheally administered with 50 mg of the mentioned dusts had hydroxyproline determined. After six months of experiment, histopathological examination of lungs was carried out. It was found that different SiO2 content (5 and 11%) with the same content of trace metals and different content of trace metals with the same SiO2 content (5%) does not affect hydroxyproline content in lungs. A significant increase in hydroxyproline level in rats' lungs was found in a group that obtained dust of the highest SiO2 content (11%) with more trace metals. Findings of histopathological examinations confirmed the data obtained from hydroxyproline levels measurements. It seems that compounds of certain metals, such as: nickel, chromium, vanadium, at a specific SiO2 level in the dust may increase its fibrogenic properties in lungs.

[Biological testing of fibrogenic effect of dust from the "Gliwice" mine on the lung tissue]. / Biologiczny atest zwlókniajacego dzialania pylu z kopalni "Gliwice" na tkanke plucna.

Animal study was carried out to determine biological aggressiveness of mining dust by means of pulmonary tests. Dust samples, 50 mg settled dust, a mixture from 3 different mine layers (sample A) and 50 mg dust collected by the gravimetric method from different mine layers (sample B) were administered in two respective test groups by a single intratracheal injection. Silica content, determined according to Polezhayev, was found to range from 4.6% (sample A) to 12.7% (sample B). In months 3 and 6 of the experiment lung content of hydroxyproline was determined following Stegemann. Biochemical tests for hydroxyproline content revealed highest increase in the lungs of Group 2 animals 6 months after the onset of the experiment (10.312 mg). Very similar result was obtained in Group 1, with injected settled dust mixture: hydroxyproline level amounted to 10.214 mg. Both sample A and sample B induced elevated level of lung hydroxyproline although silica content in dust sample differed considerably. The study revealed that the biological aggressiveness of settled dust was not proportionate to the content of pure silica. It is thought that increased fibrogenic potentials of the settled dust may have resulted from defected crystalline structure of silica due to the grinding of the mineral in a hand-mill.