[A 5-year follow-up study of pneumoconiosis patients with positive autoantibody].

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.

Loss of regulatory characteristics in CD4+ CD25+/hi T cells induced by impaired transforming growth factor beta secretion in pneumoconiosis.

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+ CD25hi 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)-ß expression. Regarding the CD4+ CD25hi 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-ß 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-ß 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-ß. Together, these data indicated a potential pathway for the progression of pneumoconiosis through a loss of Foxp3+ Treg cells associated with impaired TGF-ß secretion.

Pathology of Sarcoidosis.

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.

COPD and levels of Hsp70 (HSPA1A) and Hsp27 (HSPB1) in plasma and lymphocytes among coal workers: a case-control study.

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.

[The expression of vascular endothelial growth factor antibody in serum of coal workers with pneumoconiosis].

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.

Man-made mineral fibers and interstitial lung diseases.

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.

[Correlation analysis between cytokines levels in serum and bronchoalveolar lavage fluid, blood T cell subsets and pneumoconiosis severity].

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.

How to improve the hygienic quality of forages for horse feeding.

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.

Hypersensitivity pneumonitis and related conditions in the work environment.

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.

Dysregulation of the immune system caused by silica and asbestos.

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.

Respiratory health effects and immunological response to Thermoactinomyces among sugar cane workers in Nicaragua.

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.

Induction of chronic inflammation in mice treated with titanium dioxide nanoparticles by intratracheal instillation.

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.

Neopterin as a marker for immune system activation in coal workers' pneumoconiosis.

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.

Exposure to silica and risk of ANCA-associated vasculitis.

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.

Induced sputum as an additional tool in the identification of metal-induced sarcoid-like reaction.

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.

[Immunological aspects of modern forms of pneumoconioses]. / Immunologicheskie aspekty sovremennykh form pnevmokoniozov.

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.

Cytogenetic damage and cell-mediated immunity in pneumoconiosis.

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.