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Phospholipid content of bronchoalveolar lavage fluid in granite workers with silicosis in Quebec.

BACKGROUND: Some of the prominent features of silicosis are hyperplasia and hypertrophy of epithelial type II cells, which in experimental animals are often accompanied by accumulation of phospholipids in the lung. METHODS: The total phospholipid content of lung lavage fluid and its composition in 28 granite stone cutters with long term exposure to silica dust (23 with radiological silicosis) was compared with that of lavage fluid in 15 normal volunteers, 15 patients with untreated idiopathic pulmonary fibrosis, and 19 patients with untreated stage 2 or 3 sarcoidosis. All lavage fluid was obtained at the time of first pulmonary investigation, which also included lung function tests. RESULTS: In the normal subjects total phospholipid content was 1.13 (0.16) micrograms phosphorus/ml of lung lavage, in the patients with idiopathic pulmonary fibrosis 0.52 (0.07) microgram/ml (p < 0.05), and in the patients with sarcoidosis 1.02 (0.20) microgram/ml composition being in the range reported in humans. In the patients with silicosis total phospholipid content was significantly decreased to an average of 0.46 (0.08) microgram/ml compared with the findings in normal subjects and patients with sarcoidosis. Within the group exposed to silica changes in total phospholipid content did not correlate with the severity of the radiographic disease, changes in lung function, the cellularity of lung lavage fluid, or hyaluronate concentrations. The secretory capacity of rat epithelial type II cells was not significantly different when cultured with bronchoalveolar lavage fluid from all four groups of subjects. CONCLUSIONS: Total phospholipid content in lung lavage fluid was significantly reduced in granite workers with radiological evidence of lung disease, but showed no correlation with radiological or functional markers of disease severity.

Adolescent↗

Silicosis in 76 men: qualitative and quantitative CT evaluation--clinical-radiologic correlation study.

PURPOSE: To use qualitative and quantitative computed tomography (CT) to test the hypothesis that impaired lung function with silicosis is due to progressive massive fibrosis (PMF) and associated emphysema. MATERIALS AND METHODS: Seventy-six men with silicosis underwent volumetric and thin-section CT of the thorax. Lung function, Borg scale dyspnea grade, silica exposure duration, and cigarette consumption were determined. Nodular profusion (NP) at chest radiography was graded according to the International Labor Organization radiographic classification system; NP and PMF at CT were visually graded by using five-point (ie, grades 0-4) and four-point (grades 0-3) scales, respectively. Emphysema and NP, which together are defined as the NP index, were quantified by using attenuation threshold values of less than -950 HU and greater than -100 HU, respectively. Mean lung attenuation was also determined. Relationships among the CT, chest radiographic, and clinical parameters were analyzed by using Spearman correlation. RESULTS: NP at chest radiography correlated (r > 0.50) with all CT parameters of nodularity. CT PMF had the highest correlation with emphysema (r = 0.58, P <.001). NP at chest radiography and all CT parameters were inversely related to lung function. At multiple regression analysis, PMF and emphysema index (both at CT) were significant determinants of forced expiratory volume in 1 second (FEV1) (P =.006 and.03, respectively) and FEV1 to forced vital capacity (FVC) ratio (P =.007 and.02, respectively). Mean lung attenuation remained related to FVC (P =.03), diffusing capacity of lung for carbon monoxide (P =.04), and Borg scale grade (P =.01). Cigarette consumption and silica exposure duration had no independent effects on lung function. CONCLUSION: Qualitative and quantitative CT parameters can be used as indirect measures of functional impairment in silicosis. PMF and emphysema are independently related to airflow obstruction, whereas mean lung attenuation is related to clinical dyspnea and reduced lung volume.

Adult↗

Pleural disease in silicosis: pleural thickening, effusion, and invagination.

PURPOSE: To retrospectively evaluate pleural disease on images from patients with autopsy-proved silicosis. MATERIALS AND METHODS: The study had institutional review board approval, and informed consent from relatives of diseased subjects was waived. Lung specimens were obtained at autopsy in 110 men (mean age, 72 years) who had been followed up radiologically for a mean of 14.8 years. Computed tomographic (CT) scans obtained within 2 years before death were examined for presence of pleural thickening; shape, composition, size, and subpleural location of progressive massive fibrosis (PMF); and pleural invagination (bandlike structure between lesion and pleura). Lung specimens were reviewed and compared with CT findings. Serial chest radiographs and CT scans were reviewed for presence of pleural effusion. Association between radiographic findings and pleural invagination was analyzed with chi2 and Student t tests. Multiple logistic regression analysis was used to find predictive variables for pleural invagination. RESULTS: Pleural effusion was found in 12 (11%) patients at chest radiography and CT, and thickening was found in 64 (58%) patients at CT; the latter finding was significantly more frequent with complicated silicosis (P < .001). At CT, 128 PMF lesions were seen, 39 (30%) of which showed pleural invagination; CT scans showed pleural thickening in 36 (92%) of these 39 lesions. In 17 (44%) PMF lesions, CT scans depicted a bandlike structure that was pathologically confirmed to represent invaginated pleura in all cases. Pathologic presence of invagination was significantly associated with pleural thickening (P < .001), ipsilateral pleural effusion (P < .01), interstitial fibrosis (P < .05), and the nearness of PMF to the pleura (P < .005). Multiple logistic regression analysis showed that pleural thickening (odds ratio, 62.51; 95% confidence interval [CI]: 5.564, 70.2) and pleural effusion (odds ratio, 25.865; 95% CI: 1.992, 335.8) were significant CT variables associated with presence of pathologic pleural invagination (P = .001 and .013, respectively). Five PMF lesions had radiographic features of rounded atelectasis. CONCLUSION: Various pleural abnormalities can occur in silicosis, especially in advanced disease.

Aged↗

Silicosis: expiratory thin-section CT assessment of airway obstruction.

PURPOSE: To prospectively evaluate if findings on paired inspiratory and expiratory thin-section computed tomographic (CT) scans in patients with silicosis correlate with pulmonary function test results. MATERIALS AND METHODS: Institutional review board approval and patient consent were obtained. Thirty-seven men (mean age, 71 years; range, 53-88 years) with silicosis were included. All patients had undergone inspiratory and expiratory thin-section CT and spirometry. Silicotic nodules, large opacity, emphysema, reticular opacities, bronchiectasis, and air trapping were graded subjectively on CT images. Emphysema was quantified on these images with built-in software. CT numbers were correlated with spirometric findings by using Spearman rank correlation analyses. Ten healthy volunteers (three men and seven women; mean age, 58 years) served as control subjects. RESULTS: After exclusion of three patients with inadequate image quality, 34 patients (mean age, 70 years; range, 53-88 years) were enrolled in the study group. Spirometric values did not differ significantly between patients with simple (n = 20) and patients with complicated (n = 14) silicosis but were significantly lower in patients than in control subjects. CT findings included air trapping (n = 33), emphysema (n = 26), nodules (n = 32), bronchiectasis (n = 22), large opacity (n = 19), and reticulation (n = 5). The extent of both air trapping and emphysema correlated negatively with spirometric values; the air trapping score showed the strongest correlation (ratio of forced expiratory volume in 1 second to forced vital capacity [FVC]: rho = -0.632, P < .001; forced expiratory flow at 50% of the FVC: rho = -0.576, P = .001). Silicotic nodule, large opacity, and bronchiectasis scores did not correlate with obstructive functional impairments. CONCLUSION: In comparison with the spirometric value, the extent of air trapping proved the best CT index in the assessment of obstructive derangement in workers with exposure to silica dust.

Aged↗

Type 2 immune response associated with silicosis is not instrumental in the development of the disease.

It has been proposed that the development of lung fibrosis is associated with a T helper type 2 response, mainly characterized by IL-4 and IL-13 production. We investigated the potential role of type 2 immune polarization in the silicotic process and examined the pulmonary response to silica particles in mice genetically deficient for IL-4. We found that IL-4(-/-) mice were not protected against the development of silicosis, suggesting that IL-4 is not essential for the development of this fibrotic disease. By evaluating the intensity of silica-induced lung fibrosis in mice deficient for IL-4 receptor alpha (IL-4Ralpha), we showed that the establishment of pulmonary fibrosis was independent of both IL-4 and IL-13. Strong impairment of the type 2 immune response (IgG(1)) in the lungs of IL-4(-/-) and IL-4Ralpha(-/-) mice did not affect the development of the disease. Measurement of IL-13alpha2 receptor expression and IgG(2a), IL-12p70, and IFN-gamma levels in silica-treated IL-4(-/-) and IL-4Ralpha(-/-) animals showed that the development of silicosis was not related to an IL-13 signaling pathway or a switch to a type 1 response in deficient animals. Our data clearly indicate that the type 2 immune response associated with silicosis in mice is not required for the development of this inflammatory and fibrotic disease.

Animals↗

Mast cell basic fibroblast growth factor in silicosis.

To investigate the role of mast cells (MC) and their fibrogenic growth factors in silicosis, we performed quantitative immunohistochemistry for MC tryptase and for basic fibroblast growth factor (bFGF) in lung tissue from silicotic and control subjects. Anti-bFGF antibody was bound to lung MC, basement membrane, endothelial cells, and smooth-muscle cells. Morphometric analysis revealed that the volume density (V(v)) of MC was increased in silicotic lung and that the V(v) of bFGF-positive (bFGF(+)) cells was significantly higher than normal in silicotic lung. Most MC contained bFGF (rho = 0.88, p < 0.001). The V(v) of collagen/reticulin fibers was increased in silicosis and correlated with the V(v) of bFGF(+) cells (rho = 0.81, p < 0.001). Immature silicotic nodules contained bFGF(+) MC throughout the loose array of collagen/reticulin fibers. In large, mature nodules, the density of collagen/reticulin fibers was higher, and bFGF(+) MC were found only in the nodule periphery. Because of this circumferential MC alignment in silicotic nodules, we observed a negative correlation between the V(v) of bFGF(+) MC and the density of collagen/reticulin fibers in silicotic nodules (rho = -0.80, p < 0.001) and between the V(v) of all other nodule-associated cells and the density of collagen/reticulin fibers in the hypocellular nodule centers (rho = -0.84, p < 0.001). We conclude that MC that produce bFGF may play an important role in the development of silicosis.

Aged↗

T-lymphocyte activation in the enlarged thoracic lymph nodes of rats with silicosis.

Silicosis is primarily a mononuclear cell inflammatory and fibrotic disease of the pulmonary parenchyma. It is known that lung-associated lymph nodes are also affected. To study the involvement of lymphocytes in silicosis, we examined lymph nodes of rats 12 months after an 8-day silica aerosol exposure. We found that 2 thoracic lymph nodes close to the thymus were enormously enlarged in silicotic rats and contained a 49-fold higher cell number than control lymph nodes. The higher cell number was caused by parallel increases in T- and B-lymphocytes, natural killer (NK) cells, and macrophages without change in the relative proportions when compared with control thoracic lymph nodes. By examining interleukin-2 (IL-2) receptor and intercellular adhesion molecule-1 expression, we detected a significantly higher percentage of activated CD8+ T cells and, to a lower degree, of CD4+ T cells in thoracic lymph nodes of silicotic animals. In contrast, no differences in the activation state were found in T cells obtained from cervical or mesenteric lymph nodes of silicotic and control rats. The occurrence of activated T cells in thoracic lymph nodes of silicotic rats was documented further by selectively enhanced interferon-gamma (IFN-gamma) mRNA expression in the absence of IL-2 and IL-4 mRNA changes. These data show that T-lymphocytes of thoracic lymph nodes have become activated with an enhanced IFN-gamma gene transcription which may be an important cause of macrophage activation during silicosis.

Animals↗

Enhanced release of prostaglandin E2 from macrophages of rats with silicosis.

The pathogenesis of silicosis results, in part, from interactions between silica particles and alveolar macrophages (AM) with release of cytokines and other mediators. Different arachidonic acid metabolites have been shown to promote or to suppress inflammation and fibrosis. We designed experiments to study the production of cyclooxygenase metabolites and tumor necrosis factor-alpha (TNF-alpha) from macrophages during active silicosis. Macrophages were harvested from rats 5 to 7 mo after an 8-day silica aerosol exposure. Upon in vitro culture of AM, the spontaneous release of prostaglandin E2 (PGE2), thromboxane B2 (TXB2), and prostaglandin D2 (PGD2) of silica-exposed animals was higher than that of sham-exposed animals. Moreover, AM from silicotic rats displayed an increased sensitivity to low concentrations of lipopolysaccharide (LPS, 10 ng/ml) and released copious amounts of PGE2 and TXB2. When compared with similarly enhanced release of TNF-alpha from AM of silica-exposed rats, PGE2 production occurred later and started to increase when TNF-alpha production declined. Addition of the cyclooxygenase blocker indomethacin augmented TNF-alpha production, whereas the addition of PGE2 counteracted TNF-alpha release. Also peritoneal macrophages, which did not have direct contact with silica particles, released enhanced levels of PGE2 in response to low LPS doses. We conclude that AM and other macrophages from silica-exposed rats are preactivated and display an enhanced prostanoid production that could serve anti-inflammatory or immunomodulating roles in silicosis.

Animals↗

Silicosis-induced pulmonary artery stenosis: demonstration by MR angiography and perfusion MRI.

Silicosis is a common occupational disease. We present a 64-year-old male patient suffering from symptomatic silicosis due to compression of the pulmonary arteries by enlarged hilar lymph nodes. Clinical symptoms and diagnostic imaging modalities are described, with emphasis on cross-sectional imaging. MR angiography and perfusion MRI of the lung in silicosis are described, and their diagnostic value in pneumoconiosis is discussed.

Arterial Occlusive Diseases↗

The recognition of silicosis: labor unions and physicians in the Chilean copper industry, 1930s-1960s.

By the late 1930s, silicosis had become one of the most important occupational diseases in Chile. It was a medical and scientific problem, and a favorite topic in medical congresses; in Chile, a mining country, it also had serious political and economic implications. The recognition of silicosis did not happen in a vacuum, but was part of a national debate on the social role of the state and its responsibility toward working people's health and safety. This article traces the history of silicosis as an occupational disease from the late 1930s to the late 1960s, and argues that the recognition of the disease was the result of a medical, labor, and political struggle.

Chile↗

Initial experience on rifampin and pyrazinamide vs isoniazid in the treatment of latent tuberculosis infection among patients with silicosis in Hong Kong.

OBJECTIVE: To compare the adverse effects and treatment adherence between 2 months of rifampin plus pyrazinamide (2RZ) and 6 months of isoniazid (6H). BACKGROUND: Patients with silicosis in Hong Kong are at high risk of acquiring tuberculosis. A previous study showed that treatment with 6H reduced the risk of silico-tuberculosis by one half. METHOD: Patients with silicosis and a Mantoux skin test reaction > or =10 mm were randomized to receive either 2RZ or 6H daily. Liver function testing was done monthly during the initial 2 months. The adverse effects and treatment adherence were compared between the two regimens. RESULTS: Forty patients (mean age, 61.6 +/- 9.1 years) and 36 patients (mean age, 57.6 +/- 9.7 years) were randomized to the 2RZ and 6H arms, respectively (p > 0.05) [+/- SD]. Baseline characteristics were comparable. Nineteen patients in the 2RZ arm had peak alanine transaminase (ALT) levels > 1.5 times the upper limit of normal (ULN) in comparison with only five study subjects of the 6H arm (47.5% vs 13.9%, p < 0.01). Fourteen patients (35%) in the 2RZ arm and 1 patient (2.8%) in the 6H arm had peak ALT levels more than five times the ULN (p < 0.001). Only seven patients had symptoms suggestive of hepatitis; none of the patients had jaundice. All recovered after withholding treatment. In the 2RZ study arm, none of the baseline characteristics predicted hepatotoxicity. Other adverse effects were generally mild and comparable between both study arms. Treatment was stopped prematurely in 45% and 36.1% of patients in the 2RZ and 6H arms, respectively (p = 0.43). The main reasons were hepatotoxicity for the 2RZ arm and voluntary withdrawal after experiencing other minor adverse effects for the 6H arm. CONCLUSION: A higher incidence of hepatotoxicity was associated with rifampin plus pyrazinamide than isoniazid in the treatment of latent tuberculosis infection among patients with silicosis in Hong Kong.

Aged↗

Function of lymphocytes and monocytes in silicosis.

The function of lymphocytes and monocytes was compared in a group of 18 ex-sandblasters with silicosis and 19 control subjects. Previously noted depressed lymphocytic proliferation in response to low concentrations of concanavalin A (ConA) in subjects with silicosis was not due to factors in the serum nor correctable by supplementation with allogeneic lymphocytes. Monocytes from the peripheral blood of the subjects with silicosis responded less to a chemotactic stimulus (zymosan-activated serum) than did monocytes from normal laboratory personnel; however, there was no difference in monocytic chemotaxis when groups of similar age were compared. There was a significant correlation between age and the monocytic response to chemotactic stimuli in the studied population (laboratory personnel, silicotic subjects, and age-matched control subjects). Overall, our data suggest subtle effects of silica on selected T-lymphocytic populations involved with responsiveness to the mitogen, concanavalin A, but no effects on monocytic function. Monocytic chemotaxis is unaffected by exposure to silica but is inversely related to age.

Age Factors↗

Increased prevalence of HLA-Aw19 and of the phenogroup Aw19,B18 in advanced silicosis.

The frequencies of HLA antigens in 27 patients with silicosis were compared with those of referents matched for exposure to silica dust, age, and sex, and having no roentgenographic signs of silicosis. A group of 900 blood donors served as an additional reference group. The prevalence of HLA-Aw19 was higher in the silicosis patients (29.6 percent) than in the silica-exposed referents (3.7 percent; p = 0.02). In turn, the frequency of Aw19 in the unexposed population consisting of blood donors (19.6 percent) was higher than that of silica-exposed referents (p = 0.04). Accepting that the prevalences of HLA antigens in the blood donors fairly well describe those of the silica-exposed population, the highest risk of developing advanced fibrosis was associated with the phenotypic combination Aw19,B18 (observed-expected ratio = 17.05; p less than 0.01). The results suggest that HLA-Aw19 and the haplotype Aw19,B18 are, at least in Finnish population, associated with a progression into advanced silicotic fibrosis.

Finland↗

Value of in situ elemental microanalysis in the histologic diagnosis of silicosis.

Pulmonary specimens obtained from ten normal subjects and 53 patients with various pulmonary diseases were studied with energy-dispersive x-ray analysis. The amount of silicon in the pulmonary tissue was determined and expressed as a silicon/sulfur (Si/S) ratio. This Si/S ratio was below 0.2 in the ten normal subjects and in 14 patients who had various interstitial pulmonary diseases but had no previous history of exposure to silica or other dusts known to cause pulmonary fibrosis. The Si/S ratio was greater than 0.3 in 19 of 22 patients who had a history of exposure to silica dust and had clear-cut histologic evidence of silicosis. The Si/S ratio was less than 0.2 in 12 and between 0.2 and 0.3 in two of the 14 patients who had a history of exposure to silica dusts but no clinical or histologic evidence of silicosis. We conclude that the determination of the silicon content of tissue by energy-dispersive x-ray analysis is useful in separating the fibrosis due to silicosis from the other causes of pulmonary fibrosis.

Adult↗

CT assessment of silicosis in exposed workers.

For evaluation of the clinical usefulness of CT of the thorax in workers exposed to silica, 58 workers with long-term exposure to silica in the granite and foundry industries of the Eastern Townships of Quebec were examined. CT scans were compared with standard posteroanterior chest radiographs by using the International Labour Office 1980 grading system for silicosis. Six areas of the lung in each patient were assessed by both techniques for profusion (number) of opacities (small nodules), coalescence, and the presence of large opacities. CT scans and chest radiographs yielded similar average scores for detection of opacities. CT identified significantly more coalescence and large opacities in patients with simple silicosis. In patients with complicated silicosis, CT results were comparable with those of chest radiographs. CT of the thorax in workers exposed to silica does not identify more patients with minimal parenchymal disease, but it does detect earlier changes of coalescence.

Humans↗

A patient with asbestos-induced lung cancer complicated by silicosis.

A 76-year-old male died of lung cancer. At first, he was diagnosed as a silicosis, because he had worked for 30 years as a caster in shipyard and large opacities detected by chest x-ray and CT scanning. After the operation of lung cancer, numerous asbestos bodies were observed in the operated lung tissues. The detailed occupational inquiry revealed his asbestos use as a caster in shipyard. Early stage of asbestosis was suspected by chest CT scanning, but not definitely diagnosed in premortal examinations. Asbestosis, pleural plaques, silicosis and large cell carcinoma of the lung were histopathologically confirmed at the autopsy. A patient with asbestos-induced lung cancer complicated by silicosis was rarely published in the literature.

Aged↗

A 40-year follow-up of whetstone cutters on silicosis.

The present study, consisted of two separate surveys, was initiated to clarify the development of clinical pictures of silicosis after termination of dust exposure. The first survey was a 40-year follow-up of radiographic pictures of the chest among 200 male whetstone cutters (Group I workers). The second survey was conducted in 75 male recipients (Group II workers) of disability compensation for silicosis due to whetstone dust exposure. The study on Group I workers made it clear that the proportion of those free of radiographic findings in the chest pictures decreased during a 40-year follow-up period from 84% in the 1st health examination in 1952-6 to 36% in the 3rd examination in 1995. The rate of progression of the disease from Category 1 to 3 (after ILO-guided classification) to higher categories in a 15-year period was as high as >50%. Longer service duration and higher category of chest radiography at the previous health examination were the influential factors in determining the rapid progression of silicosis. The latter observation was confirmed also through a similar analysis on Group II workers. Whetstone preparations contained SiO2 by about 50%. No industrial hygiene data were available for both groups of stone cutters, but the exposure of Group I workers was estimated to be about 1 mg/m3, or well in excess of the current occupational exposure limit.

Adolescent↗

Does long-term concrete work cause silicosis?

The machining of cast concrete often produces heavy exposure to respirable silica dust. Work with concrete in general results in considerably less exposure, however, and only a few cases of silicosis due to work with concrete have been reported. Telephone interviews with detailed questions on occupational history were made with 271 construction workers specializing in concrete work for more than 20 years, and exposure data were evaluated for different work tasks. The mean cumulative exposure of subjects to silica was estimated to be 2.4 mg.years.m-3. Chest radiographs were classified according to the International Labour Office classification. There was no suspicion of silicosis for any of the workers. The risk of contracting silicosis from work with concrete in the Swedish construction industry in recent decades is considered to be slight and does not justify general, periodic chest radiographic screening.

Construction Materials↗