Experimental study on the effect of Si and P ion content in SiO2 exposure environment on the degree of pulmonary fibrosis.

BACKGROUND: Silicosis is a public health issue in developing countries for long and cannot be completely cured. OBJECTIVE: To study the changes of ion content with TNF-α and TGF-ß expression in alveolar lavage fluid (BALF) at different time points in rats exposed to silica and to investigate their correlation with pulmonary fibrosis. METHODS: 42 rats were randomly divided into control group (n = 12) and exposure group (n = 30). Tissues of right lower lungs were collected and fixed for further Hematoxylin-eosin (HE) and Masson staining. We collected the BALF to examine the inflammatory cytokines of TNF-α and TGF-ß and measured the ion contents in BALF. RESULTS: The increase of TNF-α level was earlier than TGF-ß. The content of silica in BALF was significantly increased after exposure and reached the maximum at 7th day, similar to the curve of cytokine TGF-ß level. However, phosphorus ions increased quickly after gradual decline of silicon ion and roughly proportional to the curve of degree of fibrosis. CONCLUSIONS: Crystalline silica exposure can cause changes in TGF-ß and TNF-α in BALF and accompanied with fibrosis and ions content variation. The abnormal expression of phosphorus ion may have significance in the occurrence and development of silicosis.

miR-138 inhibits epithelial-mesenchymal transition in silica-induced pulmonary fibrosis by regulating ZEB2.

Silica dust is a common pollutant in the occupational environment, such as coal mines. Inhalation of silica dust can cause progressive pulmonary fibrosis and then silicosis. Silicosis is still one of the most harmful occupational diseases in the world, so the study of its pathogenesis is necessary for the treatment of silicosis. In this study, we constructed a mouse model of pulmonary fibrosis via intratracheal instillation of silica particles and identified the decreased expression of miR-138 in fibrotic lung tissues of mice. Moreover, the overexpression of miR-138 retarded the process of epithelial-mesenchymal transition (EMT) in a mouse model of silica particles exposure and epithelial cells stimulated by silica particles. Further studies showed that ZEB2 was one of the potential targets of miR-138, and the up-regulation of miR-138 reduced ZEB2 levels in mouse lung tissues and in epithelial cells. We next found that the expression levels of ɑ-SMA and Vimentin were significantly increased and E-cadherin levels were decreased after transfection with miR-138 inhibitor in epithelial cells. However, these effects were abated by the knockdown of ZEB2. Consistently, the increased migration ability of epithelial cells by miR-138 inhibitor transfection was also reversed by the knockdown of ZEB2. Collectively, we revealed that miR-138 significantly targeted ZEB2, thus inhibited the EMT process and mitigated the development of pulmonary fibrosis. miR-138 may be a potential target for the treatment of pulmonary fibrosis.

Alpha-lipoic acid attenuates silica-induced pulmonary fibrosis by improving mitochondrial function via AMPK/PGC1α pathway activation in C57BL/6J mice.

Silicosis is characterized by pulmonary interstitial fibrosis that arises as a result of chronic exposure to silica. The few available treatments only delay its progression. As α-lipoic acid (ALA) has been shown to have various beneficial effects, including mitoprotective, antioxidant, and anti-inflammatory effects, we hypothesized that it may exhibit therapeutic effects in pulmonary fibrosis. Therefore, in the present study, we used a murine model of silicosis to investigate whether supplementation with exogenous ALA could attenuate silica-induced pulmonary fibrosis by improving mitochondrial function. ALA was administered to the model mice via continuous intragastric administration for 28 days, and then the antioxidant and mitoprotective effects of ALA were evaluated. The results showed that ALA decreased the production of reactive oxygen species, protected mitochondria from silica-induced dysfunction, and inhibited extracellular matrix deposition. ALA also decreased hyperglycemia and hyperlipidemia. Activation of the mitochondrial AMPK/PGC1α pathway might be responsible for these ALA-mediated anti-fibrotic effects. Exogenous ALA blocked oxidative stress by activating NRF2. Taken together, these findings demonstrate that exogenous ALA effectively prevents the progression of silicosis in a murine model, likely by stimulating mitochondrial biogenesis and endogenous antioxidant responses. Therefore, ALA can potentially delay the progression of silica-induced pulmonary fibrosis.

A 67-Year-Old Woman With Progressive Dyspnea and Innumerous Pulmonary Nodules.

CASE PRESENTATION: A 67-year-old woman, who recently immigrated to the United States from Afghanistan, presented to the hospital after sustaining a mechanical fall. She had no significant medical history and was not on any medication routinely. She denied any fever, night sweats, weight loss, shortness of breath, or hemoptysis. The patient had no prior personal history or exposure to TB. Results of a previous purified protein derivative skin test upon immigration were negative.

Distinct metabolic features in the plasma of patients with silicosis and dust-exposed workers in China: a case-control study.

BACKGROUND: Silicosis is a progressive pneumoconiosis characterized by interstitial fibrosis following exposure to silica dust. The role of metabolic dysregulation in the pathogenesis of silicosis has not been investigated in detail. This study aimed to identify different metabolic features in the plasma of patients with silicosis and dust-exposed workers without silicosis in metabolomics studies. METHODS: Patients with silicosis, dust-exposed workers (DEWs) without silicosis and age-matched healthy controls were recruited in a case-control study. The metabolomics analyses by ultra-high performance liquid chromatography-mass spectrometry were conducted. Distinct metabolic features (DMFs) were identified in the pilot study and were validated in the validation study. The enriched signalling pathways of these DMFs were determined. The ability of DMFs to discriminate among the groups was analysed through receiver operating characteristic (ROC) curves. The correlations between DMFs and clinical features were also explored. RESULTS: Twenty-nine DMFs and 9 DMFs were detected and had the same trend in the pilot study and the validation study in the plasma of the DEW and silicosis groups, respectively. Sphingolipid metabolism was the major metabolic pathway in the DEWs, and arginine and proline metabolism was associated with silicosis. Twenty DMFs in the DEWs and 3 DMFs in the patients with silicosis showed a discriminatory ability with ROC curve analysis. The abundance of kynurenine was higher in Stage III silicosis than in Stage I or Stage II silicosis. L-arginine and kynurenine were both negatively correlated with the percentage of forced vital capacity predicted in silicosis. CONCLUSIONS: Distinct metabolic features in the plasma of DEWs and the patients with silicosis were found to be different. Sphingolipid metabolism and arginine and proline metabolism were identified as the major metabolic pathway in the DEW and silicosis groups, respectively. L-arginine and kynurenine were correlated with the severity of silicosis.

SiO2 stimulates macrophage stress to induce the transformation of lung fibroblasts into myofibroblasts and its relationship with the sphingomyelin metabolic pathway.

Silicosis is a serious occupational disease with the highest incidence in China. However, its pathogenesis has not been fully elucidated. Studies have shown that the sphingomyelin signaling pathway may play an important role in different fibrotic diseases but its role in silicosis-mediated fibrosis is still unclear. In this study, the supernatant of human peripheral blood mononuclear cell line (THP-1)-derived macrophages exposed to silica (SiO2 ) was used to stimulate the transformation of human embryonic lung fibroblast cell line (HFL-1) into myofibroblasts, and the intervention effect of recombinant human acid ceramidase (rAC) was observed. The results showed that SiO2 stimulated the production of reactive oxygen species and malondialdehyde in the supernatant of THP-1-derived macrophages and increased the secretion of TGF-ß1, TNF-α, and IL-8. In addition, we found that the expression levels of α-SMA, FN, Col I, and Col III in HFL-1 cells increased. Meanwhile, the activities of ASMase and ACase and the expression levels of Cer, Sph, and S1P were increased. Intervention by rAC can suppress these changes to different degrees. In conclusion, the present study shows that SiO2 dust poisoning may stimulate HFL-1 cell differentiation into myofibroblasts by inducing oxidative stress in THP-1-derived macrophages, thereby promoting the secretion of a variety of inflammatory factors and activating the sphingolipid signaling pathway in HFL-1 cells. Exogenous rAC can effectively interfere with the stimulation of HFL-1 cells by silica in vitro.

The UFSP2/UFMylation Pathway Is Involved in Silica-Induced Pulmonary Injury.

Silicosis is an irreversible occupational pulmonary disease that is characterized as progressed pulmonary fibrosis. In this study, we investigated the changes of UFSP2 and the related UFMylation in silica-induced pulmonary injury mice models. The experimental silicosis models were prepared by intratracheal injection of silica particles, and the lung samples were harvested at the first or the seventh day after treatment. We found that the UFSP2 expression in the 1-day models was comparable, whereas it was upregulated in the 7-day models. Consistently, the UFMylation in the lung tissues of the 7-day models was activated. In addition, we observed the CADM2, an adhesion molecule, was reported to associate with epithelial-mesenchymal transition, was upregulated in the lungs of 7-day models. In contrast, it remained comparable in the 1-day models. Our data indicated that the UFSP2/UFMylation pathway and the CADM2 might be involved in the silica-induced pulmonary injury.

The role of macrophage-derived TGF-ß1 on SiO2-induced pulmonary fibrosis: A review.

Silicosis is an occupational fibrotic lung disease caused by inhaling large amounts of crystalline silica dust. Transforming growth factor-ß1 (TGF-ß1), which is secreted from macrophages, has an important role in the development of this disease. Macrophages can recognize and capture silicon dust, undergo M2 polarization, synthesize TGF-ß1 precursors, and secrete them out of the cell where they are activated. Activated TGF-ß1 induces cells from different sources, transforming them into myofibroblasts through autocrine and paracrine mechanisms, ultimately causing silicosis. These processes involve complex molecular events, which are not yet fully understood. This systematic summary may further elucidate the location and development of pulmonary fibrosis in the formation of silicosis. In this review, we discussed the proposed cellular and molecular mechanisms of production, secretion, activation of TGF-ß1, as well as the mechanisms through which TGF-ß1 induces cells from three different sources into myofibroblasts during the pathogenesis of silicosis. This study furthers the medical understanding of the pathogenesis and theoretical basis for diagnosing silicosis, thereby promoting silicosis prevention and treatment.

Alteration of thiol disulfide homeostasis and ischemia-modified albumin levels as indicators of oxidative status in patients with silicosis.

The aim of this study was to evaluate the oxidative status in patients with silicosis by detecting dynamic thiol disulfide homeostasis (TDH), ischemia-modified albumin level (IMA) catalase (CAT) activity, and the correlation of these markers with pulmonary function tests. Male ceramic workers with silicosis (n = 91) and healthy individuals (n = 47) were recruited for the study. Radiographic abnormalities of pneumoconiosis were classified into three profusion categories (categories 1, 2, and 3), and patients with silicosis, those with category 1, were defined as group 1 and those with category 2 or 3 were defined as group 2. Plasma levels of native thiol (NT), total thiol (TT), disulfide (Ds), IMA, and CAT activities were determined. Pulmonary function tests of groups were compared. NT, TT, and NT/TT ratios were significantly lower in groups 1 and 2 than the control group (p < 0.05). These did not differ between patients with silicosis (groups 1 and 2) and control group (p = 0.421). Ds/NT and Ds/TT ratios were significantly higher in group 2 than the control group (p < 0.05). NT, TT, and Ds did not differ significantly between groups 1 and 2. The oxidant biomarker IMA was higher (p < 0.001), and the antioxidant parameters albumin and CAT were lower in groups 1 and 2 (p < 0.001) compared with the control group. The mean FEV1act, FVCact, forced expiratory volume in 1 second/forced vital capacity (%), and value of 25-75 percent maximum expiratory flow were significantly lower in groups 1 and 2 than control group. We have used a novel colorimetric method to assess TDH in patients with silicosis. Alteration of plasma thiol/disulfide homeostasis and IMA levels might be novel indicators of oxidative stress in silicosis.

N-Acetyl-Seryl-Asparyl-Lysyl-Proline regulates lung renin angiotensin system to inhibit epithelial-mesenchymal transition in silicotic mice.

Silicosis is a major public health concern with various contributing factors. The renin-angiotensin system (RAS)is a critical regulator in the pathogenesis of this disease. We focused on two key RAS enzymes, angiotensin-converting enzyme (ACE) and angiotensin-converting enzyme 2 (ACE2), to elucidate the activation of the ACE-angiotensin II (Ang II)-angiotensin II receptor 1 (AT1) axis and the inhibition of the ACE2-angiotensin-(1-7) [Ang-(1-7)]-Mas receptor axis in C57BL/6mice following SiO2 treatment. Silica exposure caused nodule formation, pulmonary interstitial fibrosis, epithelial-mesenchymal transition (EMT), abnormal deposition of extracellular matrix, and impaired lung function in mice. These effects were attenuated by the inhibition of ACE (captopril), blockade of the AT1(losartan), or systemic knockdown of the Ace gene. These effects were exacerbated by the inhibition of ACE2 (MLN-4760), blockade of the Mas (A779), or knockdown of the Ace2 gene. N-Acetyl-Seryl-Asparyl-Lysyl-Proline (Ac-SDKP), an anti-fibrotic peptide, ameliorated the silica-exposure-induced pathological changes by targeting the RAS system by activating the protective ACE2-Ang-(1-7)-Mas axis and inhibiting the deleterious ACE-Ang II-AT1 axis, thereby exerting a protective effect. This was confirmed in mouse lung type II epithelial cells (MLE-12) pretreated with Ang II and/or gene silencing separately targeting Ace and Ace2.The effects of Ac-SDKP were similar to those produced by Ace gene silencing and were partly attenuated by Ace2 deficiency. These findings suggested that RAS plays critical roles in the pathomechanism of silicosis fibrosis and that Ac-SDKP regulates lung RAS to inhibit EMT in silicotic mice and MLE-12 cells.

A novel pathophysiological classification of silicosis models provides some new insights into the progression of the disease.

Silicosis is caused by massive inhalation of silica-based particles, which leads to pulmonary inflammation, pulmonary fibrosis and lung dysfunction. Currently, the pathophysiological process of silicosis has not been well studied. Here, we defined the progression of silicosis as four stages by unsupervised clustering analysis: normal stage, inflammatory stage, progressive stage and fibrotic stage. Specifically, in normal stage, the lung function was normal, and no inflammation or fibrosis was detected in the lung tissue. Inflammatory stage showed a remarkable pulmonary inflammation but mild fibrosis and lung dysfunction. In progressive stage, significant lung dysfunction was observed, while pulmonary inflammation and fibrosis continued to deteriorate. Fibrotic stage revealed the most severe pulmonary fibrosis and lung dysfunction but no significant deterioration in inflammation. Since the common features were founded in both silicosis patients and rodents, we speculated that the pathophysiological processes of silicosis in patients might be similar to the rodents. Collectively, our new classification identified the process of silicosis, clarified the pathophysiological features of each stage, and provided some new insights for the progression of the disease.

Magnetic targeting increases mesenchymal stromal cell retention in lungs and enhances beneficial effects on pulmonary damage in experimental silicosis.

Silicosis is a pneumoconiosis caused by inhaled crystalline silica microparticles, which trigger inflammatory responses and granuloma formation in pulmonary parenchyma, thus affecting lung function. Although systemic administration of mesenchymal stromal cells (MSCs) ameliorates lung inflammation and attenuates fibrosis in experimental silicosis, it does not reverse collagen deposition and granuloma formation. In an attempt to improve the beneficial effects of MSCs, magnetic targeting (MT) has arisen as a potential means of prolonging MSC retention in the lungs. In this study, MSCs were incubated with magnetic nanoparticles and magnets were used for in vitro guidance of these magnetized MSCs and to enhance their retention in the lungs in vivo. In vitro assays indicated that MT improved MSC transmigration and expression of chemokine receptors. In vivo, animals implanted with magnets for 48 hours had significantly more magnetized MSCs in the lungs, suggesting improved MSC retention. Seven days after magnet removal, silicotic animals treated with magnetized MSCs and magnets showed significant reductions in static lung elastance, resistive pressure, and granuloma area. In conclusion, MT is a viable technique to prolong MSC retention in the lungs, enhancing their beneficial effects on experimentally induced silicosis. MT may be a promising strategy for enhancing MSC therapies for chronic lung diseases.

Lung function and functional exercise capacity in underground semi-precious stone mineworkers.

BACKGROUND: Semi-precious stone mining may cause occupational lung disease. The impact of inhaling silica on workers' exercise capacity has only been partially studied. OBJECTIVES: To study lung function, exercise capacity, and identify factors associated with functional impairment. METHODS: In a cross-sectional study of 193 current miners from Ametista do Sul, Rio Grande do Sul, Brazil, medical and occupational data were collected. The diagnosis of silicosis was established by the history of dust exposure and chest radiographic findings. All workers performed a spirometry and a 6-minute walk test (6MWT). RESULTS: Of the sample 51 (26.4%) had silicosis. Time working in mine was 14.7±8.7 years. Spirometry showed a normal, restrictive or obstructive ventilatory pattern in 75.1 %, 13 % and 9.3 % of the workers, respectively. The diagnosis of silicosis and length of time working in mining negatively affected lung function, although exercise capacity was preserved. In the multivariate analysis, time working in mining, diagnosis of silicosis and education remained significant for forced expiratory volume in one second (FEV1; r = 0.60; r2 = 0.36; p < 0.001) and age and height for distance in 6MWT (r = 0.66; r2 = 0.43; p < 0.001). CONCLUSIONS: Our results show impaired lung function and preserved exercise capacity in current mineworkers exposed to silica. Length of time working in mining, presence of silicosis and lower education were factors associated with reduced lung function.

Artificial stone-associated silicosis in China: A prospective comparison with natural stone-associated silicosis.

BACKGROUND AND OBJECTIVE: We recently noted a dramatic increase in the number of patients with accelerated silicosis associated with exposure to artificial stone dust. Therefore, the natural history of artificial stone-associated silicosis was compared with that of natural stone-associated silicosis. METHODS: A total of 18 patients with artificial stone-associated silicosis and 63 with natural stone-associated silicosis were diagnosed sequentially in 2018 and followed up for a period of 6-12 months. Data were collected from clinical charts. RESULTS: The median duration of exposure prior to onset of symptoms of silicosis was shorter for patients who had been exposed to artificial stone dust (6.4 vs 29.3 years, P < 0.01). Four of the 18 patients experienced rapid deterioration in lung function over the follow-up period, with declines in pre-bronchodilator FVC of 587 (210-960) mL/year and FEV1 of 625 (360-860) mL/year. GGO, PMF, emphysema and pulmonary artery widening were more frequently observed on computed tomography scans of patients with artificial stone-associated silicosis than of those with natural stone-associated silicosis. Approximately 38.9% of the patients with artificial stone-associated silicosis were lung transplant candidates and 27.8% died, both rates being significantly higher than in patients with natural stone-associated silicosis (3.2% and 0%, both P < 0.01). CONCLUSION: Compared to natural stone-associated silicosis, artificial stone-associated silicosis was characterized by short latency, rapid radiological progression, accelerated decline in lung function and high mortality.

Accelerated silicosis with bone marrow, hepatic and splenic involvement in a patient with lung transplantation.

Chronic silicosis is an entity widely described in literature. However, other types such as accelerated, acute, complicated and extrapulmonary silicosis are little documented. We present a case of accelerated extrapulmonary silicosis in a lung transplant patient in whom the diagnosis of systemic silicosis was made incidental to non-respiratory complications that occurred during follow-up. The appearance of cytopenia and liver failure led to diagnostic tests that documented the presence of silicotic granulomas in those locations. Taking into account the intensity, time of exposure, onset and development of the disease, we found a highly atypical case of accelerated extrapulmonary silicosis in which inorganic particles (presumably silica) were documented inside granulomas and macrophages of the bone marrow. With these findings, we reflect on the lack of consideration of these entities within clinical practice, their probable under diagnosis and the need to study other pathophysiological mechanisms of acquisition and dissemination of silicosis.

Functional, inflammatory and interstitial impairment due to artificial stone dust ultrafine particles exposure.

OBJECTIVE: Artificial stone dust (ASD) contains high levels of ultrafine particles (UFP <1 µm) which penetrate deeply into the lungs. This study aimed to demonstrate the direct effect of UFP in the lungs of ASD-exposed workers on functional inflammatory and imaging parameters. METHODS: 68 workers with up to 20 years of ASD exposure at the workplace were recruited from small enterprises throughout the country and compared with 48 non-exposed individuals. Pulmonary function test (PFT), CT, induced sputum (IS) and cytokine analyses were performed by conventional methods. The CT scans were evaluated for features indicative of silicosis in three zones of each lung. UFP were quantitated by the NanoSight LM20 system (NanoSight, Salisbury) using the Nanoparticle Tracking Analysis. Interleukin (IL)-6, IL-8 and tumour necrosis factor alpha (TNF-α) levels were measured by Luminex (R&D Systems). RESULTS: Thirty-four patients had CT scores between 0 and 42, and 29 of them were diagnosed with silicosis. Content of the UFP retrieved from IS supernatants correlated negatively with the PFT results (total lung capacity r=-0.347, p=0.011; forced expiratory volume in 1 s r=-0.299, p=0.046; diffusion lung carbon monoxide in a single breath r=-0.425, p=0.004) and with the CT score (r=0.378, p=0.023), and with the inflammatory cytokines IL-8 (r=0.336, p=0.024), IL-6 (r=0.294, p=0.065) and TNF-α (r=0.409, p=0.007). Raw material of ASD was left to sedimentate in water for <15 min, and 50% of the floating particles were UFP. A cut-off of 8×106 UFP/mL in IS samples had a sensitivity of 77% to predict pulmonary disease. CONCLUSIONS: This is the first demonstration of an association between UFP-related decreased PFT results, worsening of CT findings and elevation of inflammatory cytokines, which may be attributed to high-dose inhalation of UFP of ASD at the workplace.

Silica-associated lung disease: An old-world exposure in modern industries.

Despite silica dust exposure being one of the earliest recognized causes of lung disease, Australia, USA, Israel, Turkey and other countries around the world have recently experienced significant outbreaks of silicosis. These outbreaks have occurred in modern industries such as denim jean production, domestic benchtop fabrication and jewellery polishing, where silica has been introduced without recognition and control of the hazard. Much of our understanding of silica-related lung disease is derived from traditional occupations such as mining, whereby workers may develop slowly progressive chronic silicosis. However, workers in modern industries are developing acute and accelerated silicosis over a short period of time, due to high-intensity silica concentrations, oxidative stress from freshly fractured silica and a rapid pro-inflammatory and pro-fibrotic response. Appropriate methods of screening and diagnosis remain unclear in these workers, and a significant proportion may go on to develop respiratory failure and death. There are no current effective treatments for silicosis. For those with near fatal respiratory failure, lung transplantation remains the only option. Strategies to reduce high-intensity silica dust exposure, enforced screening programmes and the identification of new treatments are urgently required.

Role of Nephronectin in Pathophysiology of Silicosis.

Silicosis is a typical form of pneumoconiosis and is characterized as a type of lung fibrosis. Silica particles are captured and recognized upon by alveolar macrophages via the macrophage receptor with collagenous structure (MARCO) scavenger receptor, and thereafter the inflammasome is activated. Thereafter, various chemokines/cytokines play their roles to eventually form fibrosis. Additionally, silica particles chronically activate T helper cells which sets the background for the formation of silicosis-associated autoimmune disturbances. The occurrence and progression of lung fibrosis, the extracellular matrix-related molecules such as integrins and their ligands including fibronectin, vitronectin, laminin, and collagens, all play important roles. Here, the roles of these molecules in silicosis-related lung fibrosis are reviewed from the literature. Additionally, the measurement of serum nephronectin (Npnt), a new member of the integrin family of ligands, is discussed, together with investigations attempting to delineate the role of Npnt in silica-induced lung fibrosis. Serum Npnt was found to be higher in silicosis patients compared to healthy volunteers and seems to play a role in the progression of fibrosis with other cytokines. Therefore, serum Npnt levels may be employed as a suitable marker to monitor the progression of fibrosis in silicosis patients.

Radiological progression and lung function decrements among silica-exposed ceramic workers: a longitudinal study.

Objectives: This follow-up study set out to evaluate the natural course and radiographic progression of silicosis among ceramic workers and describe the risk factors related with disease progression. Materials and methods: We retrospectively analyzed the data of ceramic workers with silicosis who were referred to our hospital between February 2010 and March 2018. A total of 165 ceramic workers followed at least 24 months and with at least two chest radiographs were included in the study. Results: The duration of silica exposure ranged from 5.5 to 27 (median 13.6) years. The numbers of patients according to follow-up time were as follows: 38 (2-2.9) years, 77 (3-3.9) years, 26 (4-4.9) years, 17 (5-5.9) years, and 7 (≥6) years. Overall 62 of 165 (37.5%) cases showed radiologic evidences of progression ranging from 2 to 8.9 years (mean 3.7 years). Pulmonary function loss rate among silicosis patients was 36.9% (61/165). Multiple logistic regression analysis showed a significant relation between radiographic progression and age (OR, 1.079: 95% CI, 1.011-1.152), follow-up time (OR, 1.557: 95% CI, 1.144-2.118), and the ILO category (category 2 or 3) at first visit (OR, 3.507: 95% CI, 1.505-8.170). Conclusions: Our findings suggest that one-third of Turkish ceramic workers with silicosis who were followed up to 8.9 years showed progression that was related to increasing age greater ILO category at time of initial visit and follow-up duration.