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Objective: To explore the progress of small shadow and the change of lung function in pneumoconiosis with positive autoantibody, so as to provide basis for clinical treatment of pneumoconiosis. Methods: A total of 756 patients were admitted to the pneumoconiosis department of the Guangzhou Occupational Disease Prevention Hospital from January 1, 2013 to June 1, 2019. The patients with combined infection were excluded. According to whether the autoantibody was positive, they were divided into positive group and negative group, 25 cases in each group. Follow-up observation of X-ray chest radiographs, chest CT, forced expiratory volume in one second (FEV(1)) and forced expired flow at 50% of FVC (MEF(50)) of pneumoconiosis patients for 5 years, to analyze the influence of positive autoantibody on the morphology of X-ray chest film, the pneumoconiosis promotion in 5 years and lung function. Results: There were 22 males and 3 females in the autoantibody positive group, aged 53.14±10.51 years. In the autoantibody negative group, there were 23 males and 2 females, aged 53.88±8.10 years. During the 5-year observation period, there was no significant difference of small shadow shape, pneumoconiosis stage, and the pneumoconiosis promotion in 5 years between the autoantibody positive group and the autoantibody negative group ( P >0.05). However, the increment of small shadow area in the autoantibody positive group was higher than that in the autoantibody negative group ( P <0.05). FEV(1) and MEF(50) of the autoantibody positive group were significantly lower than those of the autoantibody negative group in the fourth and third years, respectively ( P <0.05). Positive autoantibody was negatively correlated with FEV(1) and MEF(50) ( P <0.05). Conclusion: The positive autoantibody can't promote the progress of X-ray, but show more small shadows on chest CT; the positive autoantibody may aggravate the decline of lung function.

Pneumoconiosis is caused by the accumulation of airborne dust in the lung, which stimulates a progressive inflammatory response that ultimately results in lung fibrosis and respiratory failure. It is possible that regulatory cells in the immune system could function to suppress inflammation and possibly slow or reverse disease progression. However, results in this study suggest that in pneumoconiosis patients, the regulatory T cells (Tregs) and B cells are functionally impaired. First, we found that pneumoconiosis patients presented an upregulation of CD4 + CD25 + T cells compared to controls, whereas the CD4 + CD25 + and CD4 + CD25 hi T cells were enriched with Th1- and Th17-like cells but not Foxp3-expressing Treg cells and evidenced by significantly higher T-bet, interferon (IFN)-γ, and interleukin (IL)-17 expression but lower Foxp3 and transforming growth factor (TGF)-β expression. Regarding the CD4 + CD25 hi T-cell subset, the frequency of this cell type in pneumoconiosis patients was significantly reduced compared to controls, together with a reduction in Foxp3 and TGF-β and an enrichment in T-bet, RORγt, IFN-γ, and IL-17. This skewing toward Th1 and Th17 types of inflammation could be driven by monocytes and B cells, since after depleting CD14 + monocytes and CD19 + B cells, the levels of IFN-γ and IL-17 were significantly decreased. Whole peripheral blood mononuclear cells and isolated monocytes and B cells in pneumoconiosis patients also presented reduced capacity of TGF-β secretion. Furthermore, monocytes and B cells from pneumoconiosis patients presented reduced capacity in inducing Foxp3 upregulation, a function that could be rescued by exogenous TGF-β. Together, these data indicated a potential pathway for the progression of pneumoconiosis through a loss of Foxp3 + Treg cells associated with impaired TGF-β secretion., (© 2017 APMIS. Published by John Wiley & Sons Ltd.)

Pathologists are frequently involved in the diagnosis of sarcoidosis on conventional biopsies or examining bronchoalveolar lavage fluid and assisting bronchoscopists when performing bronchial or transbronchial biopsies or transbronchial needle aspiration (TBNA)/endobronchial ultrasound (EBUS)-guided biopsies of enlarged lymph nodes. Histology generally does not pose difficult tasks in the correct clinical and imaging scenario, but atypical forms of sarcoidosis exist, and in these cases, the diagnosis may become difficult. When faced with granulomas in the lung, the evaluation of their qualitative features, anatomic distribution, and accompanying findings usually allows the pathologist to narrow considerably the differential diagnosis. The final diagnosis always requires the careful integration of the histology with the clinical, laboratory, and radiologic findings. How robust is the histologic component of the diagnosis varies from case to case, and the pathologist should always clearly discuss this point with the clinician; in general, the weaker the histology is, the stronger should be the clinical-radiologic findings, and vice versa. The differential diagnosis of sarcoidosis includes granulomatous infections, hypersensitivity pneumonitis, pneumoconiosis, autoimmune diseases (e.g., inflammatory bowel disease, primary biliary cirrhosis, several collagen vascular diseases (particularly Sjögren), drug reactions, chronic aspiration, and even diffuse fibrosing diseases. In this review, conventional and unusual histologic findings of pulmonary sarcoidosis are presented, highlighting the role of the pathologist and discussing the main differential diagnoses.

This case-control study aimed to investigate whether the levels of Hsp70 (HSPA1A) and Hsp27 (HSPB1) in plasma and lymphocytes were associated with the risk of chronic obstructive pulmonary disease (COPD) among coal workers. A total of 76 COPD cases and 48 age-matched healthy controls from a group of coal workers were included. The case group consisted of 35 COPD patients whose condition was complicated with coal workers' pneumoconiosis (CWP) and 41 COPD patients without CWP. Heat shock proteins (Hsps) in plasma and lymphocytes were detected by ELISA and flow cytometry, respectively. Multiple logistic regression models were applied to estimate the association between Hsp levels and COPD risk. Our results showed that plasma Hsp70 and lymphocyte Hsp27 levels were significantly higher and plasma Hsp27 levels were significantly lower in COPD cases than in controls (p < 0.01). No significant differences in lymphocyte Hsp70 levels were found between COPD cases and the matched subjects. Higher plasma Hsp70 levels (odds ratio (OR) = 13.8, 95 % confidence interval (CI) = 5.7-33.5) and lower plasma Hsp27 levels (OR = 4.6, 95 % CI = 2.0-10.5) were significantly associated with an increased risk of COPD after adjusting for confounders. Higher lymphocyte Hsp27 levels were only associated with an increased risk of COPD with CWP (OR = 6.6, 95 % CI = 2.0-22.1) but not with an increased risk of COPD without CWP (OR = 3.0, 95 % CI = 0.9-8.9). Additionally, there were strong joint effects of different Hsps on COPD risk. These results showed that higher levels of plasma Hsp70 and lower levels of plasma Hsp27 might be associated with an increased risk of COPD among coal workers. They may have the potential to serve as monitoring markers for COPD in coal workers.

Objective: To determine the role of serum VEGF-Ab in pneumoconiosis of coal workers., Methods: Four groups of participants were recruited for this study, including 230 with early stage (less serious than stage one) changes in relation to pneumoconiosis, 328 with confirmed coal worker pneumoconiosis, 309 workers exposed to coal dust, and 393 healthy people. All participants completed a questionnaire, and have their peripheral venous blood sample taken. Serum VEGF-Ab was detected by ELISA., Results: Compared with healthy controls and those with early stage changes, the participants with pneumoconiosis and those exposed to coal dust had higher levels of serum VEGF-Ab (P < 0.05). The level of serum VEGF-Ab increased with the progression of stages of pneumoconiosis but without statistical significance (P > 0.05). In those with early stage pneumoconiosis, higher levels of serum VEGF-Ab were found in their 20 yr. - and 40 yr. - compared with those in their 60 yr. - (P < 0.05). By contrast, in those with confirmed pneumoconiosis and the healthy controls, lower levels of serum VEGF-Ab were found in their 20 yr. - and 40 yr. - compared with those in their 60 yr. - (P < 0.05). In those with early stage or first-stage pneumoconiosis, longer than 25 years work experience was associated with higher levels of serum VEGF-Ahb (P < 0.05). In those with confirmed pneumoconiosis, coal mining workers had a higher level of serum VEGF-Ab than their colleagues involving in assistance tasks (P < 0.05). In those exposed to coal dust, tunnelling workers had a higher level of serum VEGF-Ab than their coal mining colleagues (P < 0.05)., Conclusion: Serum VEGF-Ab is associated with the occurrence and development of coal worker pneumoconiosis. The level of serum VEGF-Ab increases with age and length of exposure to dust.

Purpose of Review: Manufactured (artificial) fibers represent an important and continuously growing volume among substitutes to natural fibers. A major proportion of the population in an industrialized society has been, is, or will be in contact with these fibers. The fibrous configuration of asbestos is well recognized as being an important parameter in toxicity, and now that of synthetic fibers is also suspected of inducing serious health effects on the respiratory system. There is an ongoing debate about the actual fibrogenic effect of these man-made mineral fibers (MMMFs) in humans., Recent Findings: Several case reports have demonstrated the biopersistance of MMMFs in the lung of workers who were exposed to rock wool or fiberglass for long periods of time and were diagnosed with interstitial pulmonary fibrosis. A 20-year follow up also identified refractory ceramic fibers in workers' lung tissue, with significant association between cumulative fiber exposure and radiographic pleural changes. Newly emerging man-made fiber industries appear to induce new types of occupational diseases., Summary: Exposure of workers in MMMFs production plants is correlated to high risk for developing pneumoconiosis. Large epidemiological studies are needed in order to determine dose metrics for risk assessment and management.

Objective: To analyze the correlation between the pneumoconiosis severity and the cytokines levels in serum and bronchoalveolar lavage fluid (BALF) or blood T cell subsets., Methods: The subjects were divided into five groups: control group (6 cases), group exposed to dusts (6 cases) and 3 pneumoconiosis groups (36 in stage I, 12 in stage II and 10 in stage III). ELISA was used to detect IL-6, sIL-2R and TNF-α levels in serum and BALF. The subsets of blood T cells were classified by flow cytometer., Results: As compared with control group and group exposed to dusts, the levels of serum IL-6 and sIL-2R in patients with II or III stages significantly increased, which were positively correlated with pneumoconiosis stages (r(1) = 0.74, r(2) = 0.81, P < 0.05). The level of serum TNF-α significantly decreased in patients with III stages, as compared with control group and group exposed to dusts. There was a negative correlation between serum TNF-α level and pneumoconiosis severity (r = -0.58, P < 0.05). There was a positive correlation between the levels of IL-6, sIL-2R and TNF-α in BALF and the levels of IL-6, sIL-2R and TNF-α in serum (r(1) = 0.77, r(2) = 0.96 and r(3) = 0.88, P < 0.05). The proportion of CD(4)(+)T cells and the ratio of CD(4)(+)/CD(8)(+) decreased dramatically in patients with II and III stages. But there was no correlation between these values and disease severity., Conclusion: The immune function in Th cell was inhibited. The levels of IL-6, sIL-2R and TNF-α in serum and BALF were associated with the severity of pneumoconiosis.

Background: Improving the hygienic quality of forages for horse nutrition seems to be a reasonable target for decreasing the prevalence of pulmonary diseases. The aim of the experiment was to study the effects of different agricultural practices on the main aero-allergens contained in forages, including breathable dust, fungi, mycotoxins and pollens., Results: Results showed that the late harvest of hay, a second crop or a haylage production provides a good alternative to increase hygienic quality by reducing fungi contamination and breathable dust content. Barn drying of hay, while having no effect on breathable dust, similarly reduced fungi contamination. In contrast, when hay was harvested at a lower dry mass content (750 g DM kg⁻¹ versus 850 g DM kg⁻¹), both breathable dust and fungi contaminations were increased, which could at least be reversed by adding propionic acid just before baling. Zearalenone was detected in different hays, and even in one case, in breathable dust., Conclusion: Overall, our data suggest that different approaches can be used to increase forage hygienic quality for horse feeding and thus reduce their exposure to factors involved in equine pulmonary disease., (Copyright © 2011 Society of Chemical Industry.)

Hypersensitivity pneumonitis can occur from a wide variety of occupational exposures. Although uncommon and difficult to recognize, through a detailed work exposure history, physical examination, radiography, pulmonary function studies, and selected laboratory studies using sera and bronchoalveolar lavage fluid, workers can be identified early to effect avoidance of the antigen and institute pharmacologic therapy, if necessary. A lung biopsy may be necessary to rule out other interstitial lung diseases. Despite the varied organic antigen triggers, the presentation is similar with acute, subacute, or chronic forms. Systemic corticosteroids are the only reliable pharmacologic treatment but do not alter the long-term outcome., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Silica and asbestos cause pneumoconioses known as silicosis and asbestosis, respectively, that are each characterized by progressive pulmonary fibrosis. While local effects of inhaled silica particles alter the function of alveolar macrophages and sequential cellular and molecular biological events, general systemic immunological effects may also evolve. One well-known health outcome associated with silica exposure/silicosis is an increase in the incidence of autoimmune disorders. In addition, while exposure to silica--in the crystalline form--has also been seen to be associated with the development of lung cancers, it remains unclear as to whether or not silicosis is a necessary condition for the elevation of silica-associated lung cancer risks. Since asbestos is a mineral silicate, it would be expected to also possess generalized immunotoxicological effects similar to those associated with silica particles. However, asbestos-exposed patients are far better known than silicotic patients for development of malignant diseases such as lung cancer and mesothelioma, and less so for the development of autoimmune disorders. With both asbestos and crystalline silica, one important dysregulatory outcome that needs to be considered is an alteration in tumor immunity that allows for silica- or asbestos- (or asbestos-associated agent)-induced tumors to survive and thrive in situ. In this review, the immunotoxicological effects of both silica and asbestos are presented and contrasted in terms of their abilities to induce immune system dysregulation that then are manifest by the onset of autoimmunity or by alterations in host-tumor immunity.

Specific sensitization and respiratory effects associated with the inhalation of sugar cane dust were evaluated in a group of 51 Nicaraguan workers exposed to bagasse. A questionnaire interview, lung function test, serum precipitin tests for Thermoactinomyces sacchari and T. vulgaris, and immunoglobulin E tests for specific environmental allergens were performed for each worker. Twenty-one workers reported at least one respiratory symptom and 16 reported possible symptoms of bagassosis. Six workers demonstrated acute symptoms, 1 had chronic symptoms, and 9 had the reacutized form of the disease. A higher proportion of precipitin response to T. sacchari and T. vulgaris was found in workers reporting symptoms suggestive of acute bagassosis. A possible restrictive ventilatory pattern was observed in 8 subjects and a mild airway obstruction in 1 subject. Priority must be given to a surveillance and exposure prevention program for workers employed in sugar cane production and processing.

Titanium dioxide nanoparticles (TNP) are nanomaterials which have various applications including photocatalysts, cosmetics, and pharmaceuticals because of their high stability, anticorrosiveness, and photocatalytic properties. Induction of cytokines and potential chronic inflammation were investigated in mice treated with TNP (5 mg/kg, 20 mg/kg, and 50 mg/kg) by a single intratracheal instillation. Pro-inflammatory cytokines such as IL-1, TNF-a, and IL-6 were significantly induced in a dose-dependent manner at day 1 after instillation. The levels of Th1-type cytokines (IL-12 and IFN-gamma) and Th2-type cytokines (IL4, IL-5 and IL-10) were also elevated dose-dependently at day 1 and the inflammatory responses were sustained until the remainder of experimental period for 14 days. By the induction of Th2-type cytokines, the increased B cell distributions both in spleen and in blood, and increased IgE production in BAL fluid and serum were observed. In lung tissue, increase of inflammatory proteins (MIP and MCP) and granuloma formation were observed. Furthermore, the expressions of genes related with antigen presentation (H2-T23, H2-T17, H2-K1, and H2-Eb1) and genes related with the induction of chemotaxis of immune cells (Ccl7, Ccl3, Cxcl1, Ccl4, Ccl2) were markedly increased using microarray analysis. From these data, it could be suggested that TNP possibly cause chronic inflammatory diseases through Th2-mediated pathway in mice.

Coal workers' pneumoconiosis (CWP) is an occupational pulmonary disease that occurs by chronic inhalation of coal dust. Coal workers' pneumoconiosis is divided into two categories depending on the extent of the disease as simple pneumoconiosis (SP) and progressive massive fibrosis (PMF). Development of CWP is associated with the activation of the immune system. Neopterin is a predictive biochemical marker of cell-mediated immune activation and elevated levels of neopterin are detected in body fluids of patients with immune-related diseases. The present study was aimed to investigate whether increased serum, urine and bronchoalveolar lavage (BAL) fluid levels of neopterin is associated with the development and/or severity of CWP. Mean serum neopterin levels in SP and PMF patients (10.72 +/- 0.98 nmol/L; 14.08 +/- 3.86 nmol/L, respectively) were significantly higher than those of control group (5.30 +/- 0.47 nmol/L) (P < 0.05). Although urinary neopterin levels were also increased in SP and PMF patients (235.17 +/- 7.40 micromol/mol creatinine; 256.05 +/- 9.43 micromol/mol creatinine, respectively) as compared with the control group (140.00 +/- 5.43 micromol/mol creatinine) (P < 0.01), they were within the normal concentration range. No significant difference was observed between serum and urinary neopterin levels of SP and PMF patients. A correlation was observed between serum and urinary neopterin levels of all subjects (r = 0.525, P < 0.01). Bronchoalveolar lavage fluid neopterin levels were significantly higher in patients with SP and PMF (22.67 +/- 2.9 nmol/L; 41.67 +/- 8.68 nmol/L, respectively) compared with control subjects (6.264 +/- 1.74 nmol/L) (P < 0.05, P < 0.01, respectively). The levels of neopterin in BAL fluid were also significantly higher in patients with PMF than in those with SP (P < 0.05). These findings indicate that elevated serum and BAL levels of neopterin may be considered as a suitable biomarker for the assessment of CWP.

Background: Exposure to silica dust is considered to be one of etiological factors of antineutrophil cytoplasmic antibodies (ANCA) -associated vasculitis (AAV)., Methods: Subjects exposed to silica dust in Central Bohemia and followed in the Department of Occupational Medicine, Charles University, were selected for study. A group of 86 men exposed to SiO2 for at least 5 years were examined. The association between occupational exposure to silica dust and ANCA positivity is analyzed., Results: The subjects had a mean age of 66.7 years, and mean exposure to silica of 22.3 years. ANCA were detected significantly more frequently in patients group (17.1%; P-ANCA 18x, C-ANCA 3x) than in controls (n = 28, mean age 64.2 years, P-ANCA 1x, i.e., 3.6%). ANCA positivity was found less frequently (7.1%) in the group with history of SiO2 exposure without signs of pronounced silicosis, than in the group with simple (30.3%) or complicated silicosis (36.0%). Odds ratio for ANCA positivity and relative risk estimate in patients with silicosis were highly significant. Among possible predictor factors for ANCA positivity, silicosis and tuberculosis were relevant. No typical AAV was present among the patients., Conclusion: Long-term silica exposure may be one of the exogenous factors contributing to ANCA production, however, silica exposure alone, without typical silicosis, was not associated with ANCA positivity., ((c) 2006 Wiley-Liss, Inc.)

Background: Aluminium dust exposure produces asthma, chronic bronchitis, pulmonary fibrosis and granulomatous lung diseases. There is an increased risk of mistaken diagnosis of sarcoidosis when other interstitial lung diseases of known origin are occurring., Case Report: We describe a case of a welder working in a stainless steel factory who had been exposed for more than 20 years to a dusty environment containing high levels of hazardous dust. He underwent lung function studies, a beryllium-lymphocyte transformation test (BeLTT), induced sputum (IS) analysis, aluminum-induced blastic proliferation test, and mineralogical and immunologic studies. The lung function tests raised the suspicion of sarcoidosis. T cell subsets recovered from induced sputum disclosed a helper T lymphocyte alveolitis, and transbronchial biopsies showed sarcoid-like epithelioid granulomata. Peripheral blood lymphocytes exhibited blastic transformation in the presence of soluble aluminium compounds. Scanning electron microscope studies from induced sputum-retrieved material showed abundant particles of aluminum. His final diagnosis was sarcoid-like granulomatous-induced aluminium disease., Conclusion: We propose an alternative non-invasive approach to identify antigenic metals in occupational exposures.

One hundred and forty five patients with different forms of dust-induced lung disease and 57 controls having no contacts with industrial aerosols were examined. It was ascertained that clinical and functional evidence cannot predict the course of the disease and the development of infectious complications (silicotuberculosis, mechanic bronchitis). Impaired humoral immunity and nonspecific resistance in dust-induced lung disease depend on the type of disease and predispose to infectious complications. Predisposition to occupational lung diseases (pneumoconioses, mechanical bronchitis) is associated with increases in the concentrations of plasma fibronectin and serum IgA and a decrease in serum mucin antigen levels. In chronic mechanical bronchitis, there were lower activities of lysozyme and complement and elevated serum IgM and IgG concentrations. Fibronectin, total IgE and the inflammatory marker the mucin antigen 3EG5 are involved in immunological inflammation in dust-induced lung disease. It is worth of determining the factors of humoral immunity and nonspecific resistance in workers contacting with high concentrations of industrial aerosols and in patients with dust-induced diseases to make a precise assessment of the time course of changes in a pathological process and to define a risk for infectious complications.

Pneumoconioses are still a common cause of chronic lung disease. In industrialized countries, improvements in working conditions and dust control measures have led to a decrease in the incidence of severe forms of silicosis, coal worker pneumoconiosis, and parenchymal asbestosis. However, the diversity of settings in which silica and asbestos are used fuels a continued input of cases, and the burden of cases related to remote exposures is still considerable. Overall, the clinical picture of the classic pneumoconioses and their complications has not changed substantially. However, their limits and links have expanded toward systemic and connective tissue disease, idiopathic pulmonary fibrosis, and antineutrophil cytoplasmic autoantibody-positive vasculitides. Immunologically mediated occupational lung diseases have emerged, such as berylliosis and hard-metal disease. Advances in imaging, mineralogic analysis of bronchoalveolar lavage fluid, and immunologic techniques have been instrumental in describing new patterns of disease and are helpful in litigious or difficult cases.

The authors determined pneumoconiosis as a chronic diffuse or diffuse and granulomatous pneumonitis with pulmonary fibrosis. The article deals with identification of lymphocytes subpopulations through monoclonal antibodies, details peculiarities of cellular immunity in pneumoconiosis patients, contains new data on LgE-dependent inflammatory mechanisms including specific response to industrial dust allergens. Discussion covers ways of immune correction therapy and immune prophylactics in accordance with phases of body response to homotoxins produced due to exogenous dust load.

The International Agency for Research on Cancer (IARC) determined that crystalline silica inhaled from occupational sources should be classified as carcinogenic to humans and upgraded it from group 2A to group 1. It has also been found that silicosis may be associated with cancer of various organs and with autoimmune diseases. We studied both the cytogenetic effects and the influence on cell-mediated immunity of mineral dust inhalation in patients with pneumoconiosis, including silicosis. The frequency of sister chromatid exchanges and micronucleus in the pneumoconiosis group were significantly higher than in the controls, suggesting a cytogenetic influence of the occupationally inhaled dust. Alterations in the immunoregulatory T cells were observed in the pneumoconiosis groups, suggesting that inhaled mineral dust may cause immunotoxic effects. Based on these findings, we can consider that cytogenetic damages and immunoregulatory abnormalities in pneumoconiosis patients may play a role in the pathogenesis of various cancers and autoimmune diseases associated with pneumoconiosis.

Unlabelled: Suberosis--the lung disease suffered by cork industry workers--may present in the form of either hypersensitivity pneumonitis (HP) or obstructive pulmonary disease (OPD) with asthma-like symptoms or chronic bronchitis. Mast cells play an important role in pulmonary inflammation and are particularly implicated in the rapid release of mediators in bronchoconstriction and the production of cytokines and mediators of fibroblast activity. Increased numbers of mast cells are present in bronchoalveolar lavage (BAL) fluid in interstitial lung diseases, suggesting that these cells also participate in chronic inflammatory processes and in pulmonary fibrosis., Objectives: To assess the participation of mas cells in interstitial pulmonary inflammation in cork industry workers by histochemically analyzing their presence in BAL fluid. Foreseeing the possible implication of bronchoalveolar mast cells in the pathogenesis of suberosis, we also studied their relation to various signs and symptoms of the disease, to respiratory function parameters and to degree of alveolitis., Patients and Methods: Thirty-one cork industry workers with respiratory symptoms related to occupational exposure were enrolled. Occupational and case histories were taken. Physical examinations were complemented by chest X-rays, plethysmography/spirometry, fiberoptic bronchoscopy with BAL, and determination of carbon monoxide diffusing capacity (DLCO) and arterial blood gases at rest. Patient classification (20 with HP and 11 with OPD) was based on clinical and functional criteria and analysis of BAL fluid. Mast cells in cytospinned samples treated with two different stains [May-Grunwald-Giemsa (MGG) and Toluidine Blue (Tol.Bl.)] were counted by two observers and the results were compared., Main Results: Good correlation between the two staining methods was confirmed (rs = 0.86, p < 0.0001). Correlation between the two observers was also good (MGG rs = 0.86, Yol.Bl. rs = 0.87, p < 0.0001). The number of mast cells in BAL fluid was significantly higher in patients with HP [13.4 +/- 4.5 (x +/- SEM)] than in those with OPD (0.9 +/- 0.3; p < 0.002, Mann Whitney test). The subgroup of eight patients with poorer respiratory function (CV and/or DLCO < 80% of reference value) also had higher mast cell counts in BAL (19.9 +/- 7.7 versus 3.5 +/- 1.7; p = 0.002). We also saw a negative relation between mast cell counts in BAL fluid and lung function parameters: total lung capacity (rs = -0.68, p = 0.005) and DLCO (rs = -0.54, p = 0.008). Mast cell recovery from BAL fluid was positively related to severity of alveolitis in terms of total cell counts (rs = 0.62, p = 0.002), absolute lymphocyte counts (rs = 0.56, p = 0.006) and albumin levels (rs = 0.68, p = 0.003)., Conclusions: Our findings suggest that mast cells participate in interstitial lung cell response to the inhalation of organic cork dust, particularly when HP is the form of presentation. Moreover, mas cell recruitment on the alveolar surface seems to be related to the intersity of lymphocytosis and interstitial pulmonary inflammation and to lung function deterioration in affected patients.

The ILO classification of small and large opacities is the basis for the compensation of patients with pneumoconiosis. In order to validate the radiological findings, we compared the ILO classification with the gradings of pneumoconiosis in the post mortem investigation (n = 126). An ILO classification of 1/0 used as the threshold value for accepting the diagnosis of a pneumoconiosis was 100% sensitive with a specificity of 2%. With a value of 2/3 the sensitivity decreased to 60% and specificity increased to 74%. The grading of large opacities in the radiograph correlated well with the post mortem findings (rs = 0.71; p < 0.001). For accepting the diagnosis pneumoconiosis from the radiograph alone a threshold value of 1/0 is not specific. The ROC-plot revealed that specificity reached acceptable levels with an ILO classification of at least 2/3.

Clinical, epidemiological and experimental data indicate that inhaled metal dust containing cobalt may produce an interstitial lung disease termed "hard metal disease" (HMD). Some aspects of this pathology such as the lack of correlation with dose exposure, the low frequency of the disease and the presence of T cells in the inflammation site, all suggest the existence of a genetic susceptibility, possibly to an immunological response to cobalt or to self proteins modified by cobalt. Here we report that HMD is strongly associated with residue Glu-69 of the HLA-DP beta chain. All patients, except for one with a rare genotype, possessed this marker as compared to 17 out of 35 exposed unaffected individuals (p = 0.0014). These data allow us to genetically distinguish a subgroup of cobalt-exposed individuals at risk for HMD, independently from the more common allergic reaction.

The article deals with data of clinical examination using up-to-date methods of immune assay and covering 96 patients with various pneumoconioses including silicosis, silicotic tuberculosis, hypersensitivity pneumonitis. Results of the examination helped to identify clinical and immunologic features of various pneumoconioses induced by complex industrial aerosols.

Serum antibodies to soft tissue elements, levels of elastase, trypsin, trypsin inhibitor, alpha(2)-macroglobulin were measured to make a differential diagnosis of dust with nonoccupational bronchitis. For dust and nondust bronchitis titers of antibodies to collagen and elastin were different, serum enzymatic activity changed as a result of reduced concentration of trypsin and high elastase in dust bronchitis patients. Using the above results facilitates etiological diagnosis of bronchitis in workers exposed to dust by immunological methods as well as expertise of occupational bronchopulmonary pathology.

21 patients gave sera to clarify their clinical hypersensitivity towards flour proteins. 6 had dermatitis, 3 rhinitis and the others asthma. 3 patients showed a control reactivity towards the electrophoretically separated flour protein antigens while others had antibodies to flour antigen with molecular weights less than 100 kD or 80 kD in the case of rye. Reactivity towards antigens with molecular weight higher than 50 kD was typical of dermatitis patients, while the rhinitis and asthma cases' sera reacted towards lighter flour proteins in the 20-30 kD range. The procedure is simple, a random serum sample (5 ml) suffices, and it allows demonstration of sensitization to flour protein in a way which may be helpful in the evaluation of exposure and the diagnosis of allergic conditions due to flour dust, a major etiology of occupational respiratory disease.

Simultaneous study of immune state and HLA-testing was conducted for 73 patients with pneumoconiosis and 52 sufferers from dust bronchitis. The HLA antigens appeared to correlate with immune disorders in those diseases. The study revealed differences in the HLA antigens causing immune changes in pneumoconiosis and dust bronchitis. Those differences corresponded to differences between the markers of propensity to those diseases. Thus, the authors assume that formation of pneumoconiosis or dust bronchitis could depend on genetically determined variants of immune disorders.

Aerial prevalence of clinically important thermophilic actinomycetes and occurrence of precipitating antibodies against them in sera of 153 exposed workers have been reported. The study was carried out in two cane sugar mills namely, the Upper Doab Sugar Mills and the Ramala Sugar Mills, located in north-west India. In both the sugar mills, T. sacchari was the predominant species, it accounted for 55.1% and 50.3% of the total population of thermophilic actinomycetes, followed by T. vulgaris (19.7% and 23.7%), T. thalpophilus (21.1% and 17.1%), Saccharomonospora viridis (3.4% and 5.0%) and Saccharopolyspora rectivirgula (Faenia rectivirgula) (0.7% and 3.9%), respectively. Precipitating antibodies against thermophilic actinomycetes were demonstrable in 34 (22.2%) workers; T. sacchari alone accounted for 20 of the positive precipitin reactions, followed by S. rectivirgula in 10. The mean absorbance values for IgG antibody activity against T. sacchari as well as S. rectivirgula were found to be elevated significantly in the symptomatic workers than in the asymptomatic workers (p < 0.05) or unexposed controls (p < 0.001). However, the difference in IgG antibody activity was insignificant between precipitin-positive symptomatic workers and precipitin-positive asymptomatic workers. The results indicate that clinically important thermophilic actinomycetes are widely prevalent in cane sugar mills, and T. sacchari and S. rectivirgula are the major species involved in the sensitization of the bagasse workers in India.

The different pulmonary macrophage (airway macrophages, alveolar macrophages, interstitial macrophages, intravascular macrophages, pleural macrophages) are an important part of the lungs' defences against non-fibrous and fibrous particles deposited by inhalation. The first line of defence is airway macrophages and alveolar macrophages (AM) which initially interact with deposited chrysotile fibres and subsequently release a number of mediators including growth regulatory and chemotactic proteins, arachidonic acid metabolites, proteases, NO and active oxygen species, all of which can affect--also adversely--specific target cells in the lung. Mechanical clearance via the mucociliary escalator and dissolution of phagocytized fibres in the acidic milieu of the phagolysosome in pulmonary macrophages are further important functions of AM. Chrysotile appears to be more toxic or at least has the same toxicity to AM as amphibole fibres when doses of a similar mass are administered. However, on a fibre number basis chrysotile appears to be less toxic to AM. The importance of the appropriate dose parameter--i.e. fibre mass, number or surface area--needs to be considered in in vitro as well as in in vivo studies. Short chrysotile fibres are cleared from rat lungs very rapidly whereas longer ones are cleared at a much slower rate. This is due to efficient phagocytosis of short fibres by AM accompanied by dissolution in the acidic milieu of the phagolysosome. Prediction of chrysotile clearance in primate lung based on results from rat studies result in an overall retention half-time of approximately 105 days, based on which no long-term accumulation of chrysotile in the primate lung is to be expected. Long-term inhalation studies in baboons exposed to chrysotile confirm the very fast build up of a low steady-state lung burden, consistent with a pulmonary retention half-time for chrysotile of approximately 90 days. Despite the fast clearance and low pulmonary accumulation of chrysotile, the resulting effects, such as asbestosis, were found to be of the same severity in rats as those induced by amphibole exposure. In the amphibole-exposed rats, the fibre lung burden continued to increase with exposure time. The potential contamination of chrysotile with tremolite cannot explain these results since there was no increased pulmonary accumulation of fibres in the chrysotile-exposed rats. Effects due to lung particle overload are not to be expected in long-term chrysotile inhalation studies since no accumulation occurs and one needs to distinguish clearly between a volumetric overload of the AM (not occurring with chrysotile) and failed or partial phagocytosis of long fibres.(ABSTRACT TRUNCATED AT 400 WORDS)

Immune status was examined in 231 patients facing pneumoconiosis and coniotuberculosis so as to observe a dependence on pneumoconiosis type (silicosis, electric welder's pneumoconiosis), severity of the process, activity of tuberculosis. Markedly changed T and B immunity, having already appeared at initial stage of the disease, were revealed. Those changes due to the tuberculosis activity were characterized by lymphocytosis, marked functional immaturity of T lymphocytes, depressed B lymphocytes count, elevated serum Ig level.

In recent years, with the aging of patients with pneumoconiosis, autoimmune diseases as a complication have been observed. One of the reasons for this may be that autoimmune diseases are prone to develop among the elderly. On the other hand, it has been reported that dust itself, such as silica for example, has adjuvant effect. A review of the recent literature published in Japan and abroad was made to clarify the relationship between pneumoconiosis and autoimmune diseases and the following results were obtained. 1) Disorders which accompany pneumoconiosis: Scleroderma, rheumatoid arthritis, systemic lupus erythematosus (SLE), and disorders of the kidney and liver have been reported. In Japan, about 30 cases of pneumoconiosis accompanied with autoimmune diseases have been reported. In many of the reports, patients with pneumoconiosis and scleroderma have a past history of exposure to silica. In both case studies and case control studies, patients with rheumatoid arthritis and history of silica exposure are prone to develop pneumoconiosis. 2) Immunological studies of patients with pneumoconiosis: As for humoral immunity, elevation of polyclonal gamma-globulin, especially IgG, has been often reported together with high positive rate of autoantibodies such as antinuclear antibodies. In cellular immunity, decreased delayed type skin reaction and decreased CD4/8 ratio have been reported. In human leukocyte antigen (HLA) typing the elevated frequency of DR4 has been reported. In the study of BAL increased production of superoxide anion O2- by alveolar macrophages has been observed. 3) EXPERIMENTAL STUDIES: Silica is well known for its toxicity to cells and also for its adjuvant effect. In the German Democratic Republic, patients with scleroderma and history of long term silica exposure are recognized as patients with occupational disease even though pneumoconiosis is not clearly demonstrated on X-ray film. It is difficult from this review to nrake a definite conclusion regarding the relation between silicosis and autoimmune diseases. There is a need to repeat this review of the literature on autoimmune diseases and pneumoconiosis in the near future.

A comparative, preliminary study of the phagocytic capacity of polymorphonuclear leukocytes, and of the total plasma antioxidants was carried out in a group of workers professionally exposed to mineral dusts and in a group of patients with lung cancer. Both groups exhibited advanced respiratory failure stages II and III. The phagocytic capacity of polymorphonuclear leukocytes was found significantly increased in workers with pneumoconioses and moderately increased in patients with lung cancer. On the other hand, the peroxides and total plasma antioxidants exhibited great individual variations. Thus in lung cancer it was observed that peroxides had a tendency to decrease and antioxidants to increase. The individual study of the variations of these three parameters might be able to differentiate the reversible from the irreversible stages of the respiratory changes.

The antigenic HLA spectra, loci A, B and C, were explored in 102 patients suffering from pneumoconiosis of workers exposed to dust in machine building. Significant frequency differences were discovered in some antigens and their complexes (AI; A I B 8; Bw35 Cw4) between the patients and control group subjects (112 healthy persons). The patients with uncomplicated pneumoconiosis and coniotuberculosis manifested appreciable differences in the antigenic HLA spectra. The authors propose an algorithm of predicting risk at pneumoconiosis as well as risk at coniotuberculosis, resting on the results of the typing of the antigenic HLA spectra.

This review summarizes recent research bearing on the role played by cells of the immune system in the development of pneumoconiosis. Findings related to the cellular and humoral immune responses to silica and asbestos are highlighted. Experimental results from humans and animal models are integrated into our current understandings of cellular and cytokine-mediated pathways leading to the generation of immune responses that may contribute to fibrogenesis and fibrosis. Potential mechanisms leading to the generation of an immune response by particulates are discussed, together with the indirect effects of particulates on fibroblasts by way of the cytokine network in the lung. Finally, suggestions are given for future research to help further elucidate the relationships between the cellular components of the immune system of the lung and the fibroblast that lead to fibrosis.

A total of 58 patients with pneumoconiosis and 50 miners without pulmonary pathology were examined. HLA markers of the predisposition and resistance to the disease were revealed. Determination of the HLA antigens DR I and B 13 is most essential for revealing the predisposition to pneumoconiosis that of DR 5, A 9 and B 5 for revealing the disease resistance.

Two kinds of coal mine dust, low rank with high quartz (bituminous) and high rank with low quartz (anthracite), were assayed for ability to induce alveolitis and to stimulate interleukin-1 release from normal alveolar macrophages in vitro. Dust-elicited bronchoalveolar leukocytes were also assessed for their effects on macrophage-depleted splenocyte mitogenesis and their ability to produce interleukin-1. Quartz and titanium dioxide were used for comparison as toxic and inert dusts, respectively. Both coal mine dusts caused substantial release of interleukin-1 from normal alveolar macrophages in vitro and the levels were higher than those caused by quartz. Bituminous coal mine dust provoked acute but rapidly subsiding macrophage/neutrophil alveolitis which was greater than that provoked by titanium dioxide; anthracite caused less alveolitis than titanium dioxide and quartz caused large scale, persistent alveolitis. Whole bronchoalveolar leukocytes, including polymorphonuclear neutrophils, elicited by exposure to dust, were less inhibitory to lymphocyte mitogenesis than normal alveolar macrophages and bituminous coal mine dust-induced neutrophils were augmentary to lymphocyte mitogenesis; macrophages from inflamed lungs were, on the whole, inhibitory to lymphocyte mitogenesis. Alveolar macrophages from bituminous coal mine dust- or titanium dioxide-exposed lungs showed increased ability to release interleukin-1 on stimulation in vitro. These findings suggest that bronchoalveolar leukocytes elicited by coal mine dust could modulate immunity by means of interleukin-1 release and enhancement of lymphocyte proliferation.

It was determined that immunological parameters are of highest diagnostic significance: levels of lymphocytes subpopulation (T- and O-lymphocytes) and content of IgA and IgG. A new coefficient is suggested characterizing the ratio of albumin fractions to the sum of alpha 2- and nu-globulins fractions. A diagnostic complex consisting of most informative and accessible for the practical public health indicators is suggested.

Rats were exposed to clouds of the following pneumoconiotic dusts: quartz, coal-mine dust, and chrysotile asbestos at 10 or 50 mg/m3 for 8, 32, and 75 days; for comparison, rats were also exposed to the non-pathogenic dust titanium dioxide (TiO2). The bronchoalveolar leukocytes (macrophages and neutrophils) from dust-exposed and control rats were obtained by lavage and tested for their ability to migrate toward zymosan-activated serum. Varying amounts of neutrophils were present depending on the ability of the dust to cause inflammation and the length of exposure. There was a marked loss of chemotactic ability in leukocytes from rats inhaling the pneumoconiotic dusts compared with controls; TiO2-exposed leukocytes had some impairment of chemotaxis, but this was substantially less than that found with the pneumoconiotic dusts. The loss of chemotactic activity did not correlate with the percentage of neutrophils in the lavage cells except when there were very high levels of neutrophils, and there was substantial impairment of chemotaxis with negligible numbers of neutrophils, showing that macrophage chemotaxis was impaired. A phagocytic burden within the leucocytes was not sufficient alone to inhibit chemotaxis, nor was the loss of chemotactic activity due to occupied receptors, since incubation failed to restore chemotaxis. Loss to chemotactic activity by leukocytes from pneumoconiotic dust-exposed lung could be an important factor in the development of pneumoconiosis.

The application of new technology to the study of lung inflammation is providing fresh insight into the nature of the underlying reactions. This review highlights the impact of modern cell biological and molecular biological techniques on current research in this area.

Serum immunoglobulin (Ig) levels were measured in 788 coalworkers and 121 nonmining controls for comparison with the radiological category of pneumoconiosis after taking into account age and smoking habit. In addition a simple assessment of humoral immune competence was made by estimating the titre of serum antibody against the common gut commensal Escherichia coli. Smoking was found to depress serum IgA and IgM whilst levels of IgG and IgA increased slightly with age. Men with radiological signs of coalworkers pneumoconiosis (CWP) had significantly raised levels of IgA and IgG with increasing pneumoconiosis category. Even coalworkers with less than category 1 simple pneumoconiosis had raised levels of IgA, suggesting that increased production of this immunoglobulin occurs before radiologically identifiable pathological changes have occurred in the lung tissue. No association between reduced humoral immune competence and radiological category of pneumoconiosis was found. Whether high Ig levels in men exposed to coal dust are merely a passive response to dusted lung tissue or whether they indicate that an immunological process is important in the development of pneumoconiotic lesions remains uncertain.

Seventy-nine cases of Caplan's lung were typed for HLA-A and B antigens. The antigen Bw45 was present only in those patients with rheumatoid factor and was of significantly higher frequency (13.6%) when compared to a non-coal dust exposed population of 316 (1.0%). Those patients without rheumatoid factor showed an increase in HLA-A1 and B8 (58.6% and 51.7% respectively) when compared to the rheumatoid factor positive group (29.6% and 25.0% respectively). Clinical and radiological reassessment were performed on 49 of these patients who were also typed for HLA-DR antigens and properdin factor B allotypes. HLA-DR4 was raised in the rheumatoid factor positive group with rheumatoid arthritis (55.2% compared to 25.8% in the non-coal dust exposed group and 37.3% in coalworkers with normal radiographs). The HLA-DR results are comparable to those found in other studies of rheumatoid arthritis not associated with pneumoconiosis. The findings for HLA-A1, B8 and DR4, however, were not significant after correction was made for the number of antigens tested for. No particular Bf allotype was found to be associated with either the lung change or the arthritis. The induction of the pulmonary lesion in Caplan's syndrome is discussed in relation to the HLA findings.

To study the local distribution of lymphocyte subsets in inorganic dust diseases, bronchoalveolar lavage (BAL) was performed in seven patients with asbestosis, and in 13 patients with mixed dust pneumoconiosis (anthracosidero-silicosis). Lymphocyte subsets in BAL and blood were determined by the monoclonal antibodies OKT3 (pan T), OKT4 (helper/inducer), OKT8 (suppressor/cytotoxic), B1 (B-cells), OKIa (HLA-DR antigens), and Leu-7 (natural killer). The BAL lymphocytes were moderately elevated to 15 +/- 8 percent (mean +/- SD) in mixed dust pneumoconiosis, and even more markedly increased to 28 +/- 21 percent in asbestosis. The OKT4/OKT8 ratio in BAL was significantly increased to 4.5 +/- 2.1 in asbestosis, and significantly reduced to 0.9 +/- 0.8 in mixed dust pneumoconiosis. In blood, the ratio of T-cell subsets remained unchanged, though total lymphocytes were decreased in asbestosis. These results suggest altered cellular immune processes in the lungs of patients with pneumoconiosis and may indicate different immunoregulatory changes depending on the nature of the inhaled dust.